Therapeutic vaccination in patients with gastrointestinal malignancies. A review of immunological and clinical results.

Gastrointestinal (GI) malignancies are the most common types of human cancers. Despite the introduction of new cytotoxic drugs, a large proportion remains incurable. There is a great need to develop new complementary therapeutic modalities. Strategies exploiting targeted therapies are expanding. The focus of the present article is to review active specific immunotherapy (vaccination) in patients with GI malignancies. The review comprises a description of the immunogenicity of GI malignancies, various types of tumour antigens and mechanisms of action of cancer vaccines. Tumour escape from immune surveillance, vaccine strategies and adjuvants are also described. Clinical and immunological endpoints of cancer immunotherapy are outlined. Results of therapeutic vaccine trials published mainly during the last 5 years in PubMed enrolling a minimum of six patients with GI malignancies are included. Studies presented at the two last annual meetings of the American Society of Clinical Oncology are also covered. More than 2000 patients have been vaccinated with tumour antigens (self antigens). The procedure is safe and no autoimmune disorders have been observed after >4 years follow-up in a substantial number of patients. Humoral and cellular tumour antigen-specific immune responses were induced. A correlation between immune responses and prolonged overall survival was seen in several studies. The most encouraging results were noted in randomised controlled phase II/III trials including over 1300 colorectal carcinoma patients with minimal residual disease. A statistically significantly improved disease-free or overall survival was shown either in all vaccinated or in sub-groups of patients. Promising results were also reported in pancreatic and hepatocellular carcinoma. If the results of the randomised controlled trials hold true, active specific immunotherapy may provide a new promising targeted therapeutic approach in GI malignancies with minimal toxicity. Further enlarged randomised controlled studies are warranted to confirm the results, particularly in colon carcinoma with minimal residual disease.