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 a case of Hodgkin’s lymphoma in 1983.   Table 1 shows mABs approved by the FDA for cancer treatment  Dozens of new ones are in clinical trials, 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 targets for B cell malignancies and different forms of chronic lymphocytic leukemia. Each of these antigens plays a role in B and T cell activation, proliferation, and differentiation and hence targeting them attenuates cancer cell growth.  Rituximab as first-line treatment for non-Hodgkins lymphoma has produced better survival rates than other treatments.

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 US.  It has had great success against metastatic breast cancer.

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
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