Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Reviews
Year : 2008 | Month : October | Volume : 2 | Issue : 5 | Page : 1126 - 1132 Full Version

Novel Anticancer Monoclonal Antibodies


Published: October 1, 2008 | DOI: https://doi.org/10.7860/JCDR/2008/.344
SHARMA R

J&K Health Services Jammu-180004.

Correspondence Address :
Dr. Rashmi Sharma MD(Pharmacology), DMCH.J&K Health Services Jammu-180004.E.mail: rashmichams@yahoo.com

Abstract

The recent clinical success of anticancer antibodies like rituximab and trastuzumab has created great interest in antibody-based therapeutics for hematopoietic and solid tumor malignancies. The objective of this study is to review monoclonal antibodies (MAbs) used in oncology and to describe their pharmacological characteristics. Prominent general/internal medicine journals (MEDLINE, EMBASE, PUBMED between 2000 and 2007) were searched for review papers and clinical trials published on MAbs as novel anticancer drugs. These anticancer MAbs act by inducing lysis of cancer cells (rituximab, alemtuzumab), by targeting receptors involved in cell growth and proliferation of cells (trastuzumab, cetuximab, bevacizumab) and by delivering radioisotopes to cancer cells (tositumomab conjugated with I131) and cytotoxic molecule (gemtuzumab). Therapy with MAbs has been recognized as a promising therapeutic tool in the field of oncology and a large number of molecules are currently undergoing clinical trials. It is hoped that rational development of combination of multiple therapies directed at different targets, along with unique chemotherapy agents, MAbs and antisense or other cytokines will lead to more effective approaches for cancer patients.

Keywords

Rituximab, Alemtuzumab, Cetuximab, Tositumomab, Gemtuzumab.

Novel Anticancer Monoclonal Antibodies

Cancer is a disease of cell characterized by a shift in the control mechanisms that govern cell proliferation and differentiation. There have been numerous advances in the pathogenesis of cancer; as a result, significant progress has been made and is still being made in the development of novel anticancer drugs. Drugs that have recently entered development are targeted to interfere with cell differentiation, metastasis, and angiogenesis. Hypoxic tumor stem cells specific agents, radio-sensitizing agents, normal tissue radio-protecting agents and biologic response modifiers are other drugs under development. Monoclonal antibodies (MAbs) targeting the receptors of growth factors or antigens on the cell surface are an important strategy for antitumor therapy. The introduction of MAbs into the treatment of cancer has led to remarkable improvements in patient survival. The recent clinical success of anticancer antibodies like rituximab and trastuzumab has created great interest in antibody-based therapeutics for hematopoietic and solid tumor malignancies (1).

The objective of this study is to review MAbs used in oncology and to describe their pharmacological characteristics. Prominent general/internal medicine journals (MEDLINE, EMBASE, PUBMED between 2000 and 2007) were searched for review papers and clinical trials published on MAbs as novel anticancer drugs. All the data was collected and novel MAbs in use and under development as important anticancer therapies are summarized in the present article.

Strategies For The Employment Of Mabs
Immune reaction directed destruction of cancer cell, interference with the growth and differentiation of malignant cells, antigen epitope directed transport of anti-cancer agents to malignant cells, anti-idiotype vaccines, and development of engineered (humanized) mouse monoclonals for anti-cancer therapy are some of the strategies for the employment of antibodies for anti-cancer therapy(2). Moreover, a variety of different agents (e.g., toxins, radionuclides, chemotherapeutic drugs, etc.) have been conjugated to mouse and human MAbs for selective delivery to cancer cells(3).

Types Of Mabs(4)
MAbs can be obtained from [a] murine hybridomas produced by fusion of B-lymphocytes from immunized mice or rats with murine myeloma cells (Murine MAbs) or [b] these are the combinations of the antigen-binding parts of the mouse antibody with the effector parts of a human antibody ( Chimeric MAbs), e.g. infliximab, rituximab and abciximab or [c] they can be Humanized MAbs, which bind with the amino acids forming the antigen binding site of a mouse/ rat antibody part of the human antibody molecule, thus replacing its own hypervariable regions , e.g. gemtuzumab ozogamicin, trastuzumab etc. The human MAbs are less immunogenic. Engineered MAbs have the advantages of decreased immunogenicity, enhanced half-life and optimized specificity.

Mabs Used In Anticancer Therapies
(Table/Fig 1) (Table/Fig 2)

Trastuzumab (Herceptin)(4),(5),(6)
It (humanized MAb) is the first novel targeted therapy approved for routine clinical application in advanced breast cancer, with HER2/ neu protein over expression, either as single agent or in combination with chemotherapy. It is an active agent in conjunction with paclitaxel chemotherapy in relapsed breast cancer patients who express the HER2/neu protein product. Phase I and II trials conducted by the gynecological oncology group demonstrated a response rate of ~10% in patients with ovarian cancer receiving anti-HER2/neu MAb. However, the drug is under-going testing in combination with platinum- and taxane-based chemotherapy to determine its activity in ovarian cancers. New combinations with endocrine therapy are currently being evaluated. Trastuzumab is generally well tolerated. So far, considerable cardiotoxicity was seen only in combination with doxorubicin. Thus, extensive cardio-monitoring is now performed in trials assessing further chemotherapeutic partners.

Pertuzumab(4)
It is another therapeutic MAb under clinical evaluation. It binds to a different epitope on HER2/neu than trastuzumab and inhibits heterodimerization with other HER receptors. Phase I data in patients with advanced breast cancer has shown that it is well tolerated and is clinically active, suggesting that inhibition of dimerisation may be an effective anticancer strategy.

Alemtuzumab (Campath-1H)
It is a humanized antiCD52 MAb approved by US FDA in May 2001 for treatment of fludarabine refractory CLL ( Chronic lymphocytic leukemia)(5),(7).CD52 is expressed in virtually all lymphocytes at various stages of differentiation as well as in monocytes ,macrophages, eosinophils and tissues of the male reproductive system(5),(7). The highest level is expressed on T-prolymphocytic leukemia (PLL), B-cell CLL. However, haematopoietic stem cells , erythrocytes and platelets do not express this antigen and are thus spared from a direct antibody effect .The antibody remains on the surface of target cells and acts possibly by antibody- dependent cellular toxicity, complement dependent cyto-toxicity and induction of apoptosis(5),(7). However, infusion reaction, immuno-suppression and opportunistic infections present a challenge that may be overcome with altered schedules and routes of administration. Alemtuzumab has been evaluated in 50 patients with previously treated indolent lymphoma. In combination with rituximab it has produced a response in 10 out of 22 patients with CLL(8).Alemtuzumab has ability to achieve clinical remissions and to successfully purge minimal residual disease (MRD) from both blood and bone marrow in B-CLL patients(9).In a clinical trial, forty-one consecutive CLL patients underwent allogeneic hematopoietic cell transplantation after conditioning with fludarabine, melphalan and alemtuzumab(4).The alemtuzumab-based regimen showed a relatively low rate of graft versus host disease. However, transplant related mortality remains relatively high as a result of a variety of viral and fungal infections. Further studies are on to test the efficacy of reduced doses of alemtuzumab in immunosuppressedpatients(10).

Rituximab (C2B8,Rituxan ,MabThera) (7),(11),(12),(13),(14) It is a chimeric MAb against CD20 antigen present on B-cells , was approved in 1997 for treatment of relapsed or refractory low grade or follicular CD20+ B cell indolent non Hodgkin’s lymphoma (NHL) . The possible mechanism of action includes antibody- dependent cellular toxicity, complement mediated toxicity and induction of apoptosis; as well as the effects on B–cell activation and proliferation. Because of its activity, lack of cross resistance and minimal side effects ,it has now become the commonly employed therapy for B- cell malignancies ,complications of CLL or its therapy including pure red cell aplasia and fludarabine–induced immune thrombocytopenia . However, it has limited activity as a single agent in patients relapsed or refractory after prior chemotherapy. Higher response rates are seen in previously untreated patients and when combined with chemotherapy drugs. Rituximab plus IL-2 (interleukin-2) has shown activity in a small series of patients with CLL. It has proven efficacy against a wide range of b-cell malignancies, including follicular lymphoma, small lymphocytic lymphoma, marginal zone lymphoma, Waldenstrom's macroglobulinemia, mantle cell lymphoma, diffuse large-cell lymphoma and post-transplant lymphoproliferative disorders. In indolent lymphoma that has progressed after prior chemotherapy, rituximab as a single agent is associated with 50-60% response rates in the relapsed setting and 60%- 75% as front-line therapy. However, it has greatest synergy or additive effects with the anthracycline, doxorubicin. It has been added as part of sequential therapy after chemotherapy, or as a consolidation treatment in patients who have already responded to chemotherapy. Rituximab was also used with biological-response modifiers in patients with relapsed low-grade lymphoma.

Epratuzumab (hLL2, E-mab; LymphoCide, Immunomedics, Inc, Morris Plains, NJ or AMG412, Amgen ,Thousand Oaks ,CA )
(15)CD22 is a 135-kd –cell-restricted sialoglycoprotien expressed in 60%-80% of B-cell malignancies and appears to play an important role in both B-cell adhesion and activation. Moreover, being a specific marker for most neoplastic and non neoplastic B cells it is a promising agent for the treatment .In vitro, MAb against CD22 induced cell death in several burkitts lymphoma cell lines and mediated antitumor effects in animal models. Epratuzumab, a humanised antiCD22 MAb developed to reduce the potential for immunogenicity, prolong half life and increase effector potential ,has been reported in phase I/II trials to induce response in NHL. Ongoing and future studies will continue to define its therapeutic role due to the potential to improve effectiveness in combination with chemotherapy as compared to the standard regimens.

Anti-Cd23(Idec-152,Idec Pharmaceuticals)(7)
Since CD23 expression is a characteristic feature of CLL cells ,there is a role of anti-CD23 antibody ,which is a primatized MAb ,made from a primate source with strong similarity to the human antibody . It inhibits IgE secretion in vitro and induces apoptosis of lymphoma cell lines. Clinical trials of this antibody as monotherapy or in combination with rituximab are on going .

Apolizumab (Hu1D10)(7)
It is a MAb directed against a polymorphic determinant of HLA-DR and is present on both normal and on malignant cells from about half of the patients with lymphoid malignancies. It has been evaluated clinically and activity has been noted in phase-1 trial. The combination of Hu1D10 and rituximab is being evaluated at the National Cancer Institute .However toxicities in the form of infusional and allergic reactions as well as uremic syndrome are a matter of concern .

Cetuximab(4),(16)
It is a recombinant human/mouse chimeric epidermal growth factor receptor (EGFR) MAb. It is approved by the US FDA in February 2004 to be used in combination with irinotecan for EGFR-expressing, metastatic colorectal cancer patients, who failed to improve with irinotecan-based chemotherapy or intolerant to irinotecan-based chemotherapy. In a Phase III trial, cetuximab was administered to 329 patients (irinotecan or oxaliplatin refractory). Partial response was achieved in 10.8% of patients who received cetuximab monotherapy and 22.9% of patients who received cetuximab plus irinotecan therapy (P = 0.007). The overall response rate in two Phase II trials in EGFR-expressing, metastatic colorectal cancer refractory to irinotecan therapy with cetuximab ranged from 9% to 12%. The drug was well tolerated with proper administration precautions. Cetuximab is being evaluated in combination with radiation therapy and/or platinum in patients with squamous-cell head and neck cancer, as well as cetuximab in combination with various antineoplastic agents for non-small cell lung cancer and pancreatic cancer.

Panitumumab(4),(17)
It is the first fully human MAb that binds to EGFR. Phase III study results indicate a 46% reduction in the rate of tumor progression in patients with EGFR-positive metastatic colorectal cancer who have failed prior therapy compared with those who received best supportive care alone. It is well tolerated. However, acneiform rash is the most common dose-dependent adverse effect. Studies so far indicated a low rate of infusion-related reactions (1%, grade 3-4) with it. As it targets EGFR, which is over-expressed in lung, breast, bladder, pancreatic, colorectal, kidney and head and neck cancers, hence, it is being evaluated in renal, colorectal and non-small cell lung cancers.

Bevacizumab (Avastin)(4),(7),(18)
There is a potential role for angiogenesis in CLL since angiogenesis factors such as basic fibroblast growth factor upregulates Bcl-2 and results into delay in programmed cell death. Bevacizumab, an antivascular endothelial growth factor (antiVEnGF) Mab ,is currently being evaluated in solid tumors as well as lymphomas and may be of interest in CLL. Bevacizumab is a recombinant human MAb that inhibits the biological activities of VEnGF. It has both cytostatic and cytotoxic effects, resulting in a reduction in tumor growth and increase in median survival time and time to tumor progression. It is approved as an intravenous agent for use in the first-line treatment of metastatic colorectal cancer in combination with fluorouracil-based chemotherapy. Bevacizumab has also yielded preliminary evidence of efficacy for breast, non-small-cell lung, pancreatic, prostate, renal and hepatic cancers, as well as for melanoma and acute myelogenous leukemia.

Gemtuzumab Ozogamicin(4),(19)
It is a humanized MAb directed against CD33 linked to a calicheamicin derivative. It is a member of the enediyne family of antitumor antibiotics. It gets rapidly internalized after binding to its target, followed by the release of the potent antitumor calicheamicin derivative. It induces breaking of double-stranded DNA, resulting in apoptosis. It is approved for the treatment of elderly patients ( > 60 years) with CD33+ AML (acute myeloid leukemia) in first relapse and who are not considered candidates for cytotoxic chemotherapy. It has been used in combination with all-trans retinoic acid in the treatment of acute promyelocytic leukemia with favorable response.

Radiolabeled Anti-CD20 Antibodies
(3),(4),(20),(21) Radiolabeled antibodies such as yttrium 90-ibritumomab tiuxetian (Y90), indium 111-ibritumomab (In111) and iodine 131-tositumomab (I131sub ) are seem to be even more efficacious than MAbs in the treatment of non Hodgkin’s Lymphomas. In relapsed indolent lymphoma, response rates of up to 80% have been noted with ibritumomab tiuxetian (Y90), compared to 56% with rituximab.

Tositumomab and Iodine (I 131) tositumomab is administered in two steps. The dosimetric step determines individual patient pharmacokinetics, allowing a patient- specific dose to be calculated. This is followed by the therapeutic step, with administration of the therapeutic dose between 7 and 14 days after the dosimetric dose. HMFG1 is a murine immunoglobulin G1 monoclonal antibody developed at the Imperial Cancer Research Fund (London UK) with specificity to an epitope of polymorphic epithelial mucin, which is expressed by more than 90% of epithelial ovarian cancers and many other carcinomas. In phase I and Phase II studies antibody directed to HMFG1 (labeled with 90Y) was found to be well tolerated and efficient to prolong the survival in patients with microscopic residual disease after induction chemotherapy.

Anti-CA125 Mab(5)
MAb B43.13 is a murine MAb to the tumor- specific antigen CA-125, which is found in more than 90% of patients with late-stage ovarian cancer. MAb B43.13 binds to the circulating CA125 antigen with high affinity to form complexes that the body recognizes as foreign because the complex includes the foreign antibody. These immune-complexes result into induction of CA-125 specific antibodies, T-helper cells and cytotoxic T-cells. Administered via 20 minute intravenous infusion, low dose MAb B43.13 is well tolerated than murine MAb. The possible therapeutic value of the low dose MAb approach was serendipitously discovered in a diagnostic study with MAb B43.13, which was used as tumor-imaging agent for nuclear medicine because of its high affinity for the ovarian cancer marker CA125.In a study where technetium-99m-radiolabeled MAb B43.13 was used for the immunoscintigraphic detection of recurrent ovarian cancer, it was found that a large number of patients showed unexpectedly long survival time. Recently the utility of MAb B43.13 is being explored in various clinical applications combined with standard treatments of ovarian cancers. The data collected till date regarding effects of MAb B43.13 administered for recurrent ovarian cancer or during watchful waiting stage after surgery or chemotherapy indicate that MAb B43.13 prolongs survival and increases the time to relapse in selected patients with ovarian cancer. However, the use of MAb B43.13 has not yet been studied in conjunction with the first line therapy. Traditional thinking has discouraged this approach because the immuno-suppressive properties of first line therapy may abalate the immuno-stimulatory effects of the antibody treatment. However, the phase II data generated with MAb B43.13 in patients with recurrent disease and concurrent chemotherapy indicate that study of first line therapy could be considered. Moreover, concomitant use of chemotherapeutic agents along with MAb B43.13 resulted into induction of cytotoxic T-cells without affecting safety profile of either MAb B43.13 or chemotherapeutic agents. CA125, the ovarian cancer marker to which MAb B43.13 binds, is also found in the patients with other cancer types. Hence, MAb B43.13 has potential role in various other cancer types.

Mitumumab(4)
Mitumumab is indicated in the treatment of SCLC(small cell lung carcinoma), Melanoma and soft tissue sarcoma (CD11a).

Immunotoxins(7)
These are comprised of peptides, usually an antibody or growth factor ,linked to a toxin such as diphtheria toxin ,pseudomonas exotoxin or ricin .Anti-B4 (CD19)-blocked ricin is a halotoxin from which the binding domain has been removed and a tumor specific ligand is added .Binding to normal cells is then chemically blocked .BL22 is immunotoxin directed against CD22 and fused to truncated pseudomonas exotoxin that has been proved successful in treatment of nucleoside analog refractory hairy cell leukemia .This novel agent is being explored as a potential treatment for CLL. Fusion protein Denileukin diftitox (Ontak,Seragen, Inc, San Diego, CA) ,a diphtheria–IL-2 immunotoxin approved for the treatment of cutaneous T-cell lymphomas , is directed at a specific target IL-2 (interleukin –2 ) receptors on the surface of malignant cells and is in phase II clinical trials in CLL. Its side effects include infusion related events, a vascular leak syndrome and elevation of hepatic enzymes.
Conclusion
A combination of various novel approaches to anticancer treatment has more potential values than a single agent. However, an ideal anticancer drug should eradicate cancer cells without harming normal tissue. Till date currently available agents do not meet this criterion. Therapy with MAbs has been recognized as a promising therapeutic tool in the field of oncology and a large number of molecules are currently undergoing clinical trials. It is hoped that rational development of combinations of multiple therapies directed at different targets, along with unique chemotherapy agents, MAbs and antisense or other cytokines will lead to more effective approaches for cancer patients .

References

1.
. Ross JS, Gray K, Gray GS, Worland PJ, Rolfe M. Anticancer antibodies. Am J Clin Pathol 2003 ;119(4):472-85.
2.
. Kaur J, Badyal DK, Khosla PP. Monoclonal antibodies:Pharmacologicalrelevance.IndianJ Pharmacol 2007;39:5-14.
3.
. Bodey B, Bodey B, Siegel SE, Kaiser HE. Genetically engineered monoclonal antibodies for direct anti-neoplastic treatment and cancer cell specific delivery of chemotherapeutic agents. Curr Pharm Des 2000;6: 261-76.
4.
. Gupta N, Srivastava A. Monoclonal antibodies: Targeted therapy. Indian J Pharmacol 2006;38:390-6.
5.
. Berek JS, Schultes BC and Nicodemus CF. Biologic and Immunologic Therapies For Ovarian Cancer. J Clin Oncol 2003; 21:168s-74.
6.
. Dillman RO. Perceptions of Herceptin: A monoclonal antibody for treatment of breast cancer. Cancer Biother Radiopharm 1999;14:5-10.
7.
. Mavromatis Band Cheson BD . Monoclonal antibody therapy of chronic lymphocytic leukemia. J Clin Oncol 2003;21(9) :1874-81.
8.
. Faderl S, Thomas DA, O'Brien S. An exploratory study of the combination of monoclonal antibodies Campath- IH and rituximab in the treatment of CD-52 and CD20 positive chronic lymphoid disorders. Blood 2001;98:365.
9.
. Montillo M, Schinkoethe T, Etler T. Eradication of minimal residual disease with alemtuzumab in B-CLL patients:The need for a standard method of detection and the potential impact of bone marrow clearance on disease outcome. Cancer Invest 2005;23:488-96.
10.
. Delgado J, Thomson K, Russell N, Ewing J, Stewart W, Cook G, et al . Results of alemtuzumab - based reduced intensity allogenic transplantation for chronic lymphocytic leukemia: a British Society of Blood and Marrow Transplantation Study. Blood 2006;107:1724-30
11.
. Hainsworth JD, Litchy S, Barton JH, Houston GA, Hermann RC, Bradof JE et al. Single agent rituximab as first line and maintenance treatment for patients with chronic lymphocytic leukemia: A phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2003; 21(9): 1746-51.
12.
. Kosmos C, Stamatopoulos K, Stavroyianni N, Savaris N and Papadaki T. Anti-CD20- based therapy of B cell lymphoma: state of the art. Leukemia 2002;16: 2004-5.
13.
. Grillo-Lopez AJ, Hedrick E, Rashford M, Benyunes M. Rituximab: Ongoing and future clinical development. Semin Oncol 2002;29:105-12.
14.
. Montserrat E. Rituximab in chronic lymphocytic leukemia. Semin Oncol 2003;30: 34-9.
15.
. Leonard JP, Coleman M, Ketas JC, Chadburn A,Ely S , Furmann RR et al . Phase 1/11 trial of epratuzumab (Humanized anti –CD22 antibody ) in indolent non hodgkins lymphoma . J Clin Oncol 2003;21 :3051-9 .
16.
. Wong SF. Cetuximab: An epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. Clin Ther 2005;27:684-94.
17.
. Saadeh CE, Lee HS. Panitumumab: a fully human monoclonal antibody with activity in metastatic colorectal cancer. Ann Pharmacother 2007;41(4):606-13.
18.
. Motl S. Bevacizumab in combination chemotherapy for colorectal and other cancers. A J Health Sys Pharm 2005;62:1021-32.
19.
. Estey EH, Giles FJ, Beran M, O'Brien S, Pierce S A, Stefan H, et al . Experience with gemtuzumab ozogamicin and all-trans retinoic acid in untreated acute promyelocytic leukemia. Blood 2002;99:4222-4.
20.
. Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmaanouilides C, Joyce R, et al Randomized controlled trial of yttrium 90 labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low grade, follicular or transformed B-cell non-Hodgkins lymphoma. J Clin Oncol 2002;20:2453-63.
21.
. Davies AJ. A review of tositumomab and I131 tositumomab radioimmunotherapy for the treatment of follicular lymphoma. Expert Opin Biol Ther 2005;5:577-88.

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