Clinical Applications of Monoclonal Antibodies
Monoclonal Antibodies Approved by FDA for Clinical Use
The first monoclonal antibody used in the clinic was AB 89 against anon-Hodgkin’s lymphoma patient in 1983.7 As of today, close to 100 monoclonal antibody-based drugs are under Phase II and Phase III clinical trials, each with more efficacy and less toxicity levels (8.9) and will soon come up for FDA approval. There already a handful that has been approved for cancer treatment (Table 1), both for hematologic malignancies as well as solid tumors.
A number of antigens and their collateral monoclonal antibodies have been identified for the treatment of B cell malignancies. CD20, CD52 and CD22 are attractive targets for B cell malignancies and different forms of lymphocytic leukemia. Each one of the aforementioned antigens plays a role in B and T cell activation, proliferation and differentiation and hence targeting them attenuates cancer cell growth. (25,26) As an example, using rituximab as first-line treatment for non-Hodgkin lymphoma, one-year survival was 69% and two years survival was 67%. (27-29) The duration of response obtained is not seen in other existent forms of cancer treatment and is thus relatively impressive.
With solid tumors, cell type specificity becomes an issue as there are not many specific targets for monoclonal antibodies that are not cross-reactive with antigens on normal tissues. Trastuzumab is the most widely used monoclonal antibody against solid tumor in the USA. As an alternative first-line monotherapy, trastuzumab has demonstrated efficacy and safety in patients with metastatic breast cancer that has rarely been seen with other medicinal approaches.
|Generic name (trade name; sponsoring companies)||Target||Antibody Format||Cancer Indication|
|Rituximab (Rituxan/Mabthera; Genentech/Roche/Biogen Idec)||CD20||Chimeric IgG1||Non-Hodgkin lymphoma10,11|
|Trastuzumab (Herceptin; Genentech/Roche)||HER2||Humanized IgG1||Breast cancer12,13|
|Alemtuzumab (Campath/MabCampath; Genzyme/Bayer)||CD52||Humanized IgG1||Chronic lymphocytic leukaemia14|
|Cetuximab (Erbitux; ImClone Systems/Bristol-Myers Squibb)||EGFR||Chimeric IgG1||Colorectal cancer15,16|
|Bevacizuman (Avastin, Genentech)||VEGFA||Humanized IgG1||Colorectal, breast and lung cancer17-19|
|Panitumumab (Vectibix; Amgen)||EGFR||Human IgG2||Colorectal cancer20|
|Ofatumumab (Arzerra; Genmab/GlaxoSmithKline)||CD20||Human IgG1||Chronic lymphocytic leukemia21|
|Gemtuzumab ozogamicin (Mylotarg; Pfizer)||CD33||Humanized IgG4||Acute myelogenous leukaemia22|
|90Y-Ibritumomab tituxeta (Zevalin; Biogen Idec)||CD20||Mouse||Lymphoma23|
|Tositumomab and 131I-tositumomab (Bexxar; GlaxoSmithKline)||CD20||Mouse||Lymphoma24|