Polyvalent Vaccines Against Targeted Antigens

There are at least three reasons for the expectation that cancer vaccines or antibody products against cancer should contain multiple antigens (be polyvalent) or composed of combinations of monoclonal antibodies against multiple antigens. Heterogeneity is an essential feature of malignancy with patient to patient tumor variability and even cell to cell heterogeneity in the same tumor the norm. Heterogeneity also characterizes the immune responsiveness of immunized hosts as a consequence of a variety of known and unknown factors including previous immunologic experience and genetic background. The final basis for polyvalent antibody or vaccine is a consequence of the previous two. Anti-tumor effector mechanisms are proportional to the amount of antibody bound to the cell surface, which will in turn be proportional to the number of different antigens in the vaccine.

Researchers have screened a variety of cancers and normal tissues with 40 monoclonal antibodies against 25 carbohydrate and protein antigens that were potential target antigens for immunotherapy. The antigens expressed on at least 50% of cancer cells in at least 60% of biopsy specimens of a variety of different cancer types are demonstrated in Table 1.

With the exception of mucins such as MUC1, the epithelial cancer antigen KSA (EpCAM), prostate specific membrane antigen (PSMA) in prostate cancer, carcinoembryonic antigen (CEA) in colon cancer, and CA125/MUC16 in ovarian cancer, all of the widely expressed antigens in these cancers were carbohydrates. These results from the research at MSKCC are consistent with those from other centers. Therefore, we believe that polyvalent vaccines targeting these specific antigens will generate significant immune responses.