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.

Hematologic malignancies:

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.

Solid tumors

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.

Table 1.

Generic name (trade name; sponsoring companies) Target Antibody Format Cancer Indication
Unconjugated antibodies
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
Immunoconjugates
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