ABSTRACT
EXISTING IMMUNE INTERVENTIONS FOR CANCER A majority of cancer patients are still treated by non-specifi c, higher morbidity options (e.g., chemotherapeutic compounds and radiation) or adjuvant therapies; however, targeted therapies provide the clearest path for successful treatment and disease-free progression. Because of their high affi nity and extraordinary specifi city, immune interventions provide highly targeted anti-tumor effects when directed against target antigens that are exclusively or preferentially expressed in tumors. A powerful class of targeted therapeutics such as monoclonal antibodies (mAbs) can be directed against targets of diverse chemical composition. Therapeutic mAbs exert anti-tumor effects by killing cancer cells or preventing their proliferation. For example, upon binding their respective antigens on the surface of cancer cells, rituximab (anti-CD20) and cetuximab (anti-epidermal growth factor receptor) directly kill cancer cells by activating complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) ( 1 ). Rituximab has also been shown to induce apoptosis of cancer cells ( 2 ). Trastuzumab (anti-HER2/neu) and bevacizumab (anti-vascular endothelial growth factor) prevent tumor cell proliferation by binding to and inhibiting cell surface receptors that provide signals for tumor cell survival ( 3 , 4 ). Therapeutic mAbs have shown great promise in treating cancers, but most of the cancer patients do not qualify for these treatments due to insuffi cient biomarker expression (e.g., trastuzumab) or inconclusive data on clinical effi cacy (e.g., bevacizumab). In addition, because mAbs can only access antigens on the cell surface, only a handful of validated tumor-specifi c proteins are suitable targets for therapeutic mAbs. The identifi cation of tumor-specifi c target antigens is therefore one of the greatest obstacles to the development of new therapeutic mAbs.
