Chemotherapy and immunotherapy of colorectal cancer

Abstract

More than 50% of the patients with large bowel cancer develop disseminated disease and invariably succumb. Adjuvant chemotherapy with 5-FU and levamisole have been shown to be more efficient than 5-FU alone or in combination with cytostatics. The combination of 5-FU, leukovorin and methotrexate induces prolonged survival with a good quality of life in metastatic colorectal cancer (CRC). During the last decade tumor immunotherapy has been an alternative facilitated by isolation and large scale production of cytokines and monoclonal antibodies. The mouse monoclonal antibody (MAb) 17-1A recognizes a tumor-associated antigen (TAA), present in high concentrations on the surface of gastrointestinal tumor cells. Injections of MAb 17-1A in patients with metastatic CRC induced generation of anti-idiotypic (ab2) in 90% and anti-anti-idiotypic (ab3) antibodies in 47% of the treated patients. The development of ab3 correlated significantly with survival (mean 80 weeks) while ab3- patients survive only 38 weeks. One of 52 patients treated with MAb 17-1A is a complete remission after 66 months, 3 had minor regression and 6 had a stable disease (19% RR). Based on in vitro findings showing increased antibody-dependent cellular cytotoxicity (ADCC) by the combination of granulocyte-macrophage colony stimulating factor (GM-CSF) and MAb 17-1A, 16 CRC patients have been treated with subcutaneously injections of GM-CSF for 10 days and intravenous infusions of MAb 17-1A at day 3. Two of 16 are in CR, 1 in MR and 3 in SD (37.5% RR). Minor side-effects were registered. A further development of immunotherapy of CRC might imply vaccination by injection of specific human anti-idiotypic antibodies (ab2) which mimics the nominal antigen, in order to induce a specific immunity.