Peptide vaccine for colorectal cancer; an update

Colorectal cancer is a common disease which accounts for around half a million deaths yearly worldwide. We have performed genome-wide exploration using cDNA microarray profiling, and successfully identified a new tumor-associated antigen (TAA) that can induce potent cytotoxic T lymphocytes specific to tumor cells, ie, RNF43, KOC1, TOMM34, VEGFR1 and VEGFR2. We conducted a phase I dose escalation study and a phase II study using these five tumor-associated antigen epitope peptides for colorectal cancer patients. For a breakthrough in tumor escape mechanisms, immuno-chemo-combined therapy has been conducted. Tumor-cell killing by anticancer drugs may be attributed to their immuno- and pharmacologic effects. Chemotherapy is in fact able to upregulate tumor-associated antigen expression, and to downregulate tumor cell resistance to the death signals induced by tumor antigen-specific cytotoxic T lymphocytes. This provides the rationale for combining chemo- and immunotherapy. We conducted a phase II trial with the administration of epitope peptides alongside chemotherapy (5-fluorouracil, folinic acid, and oxaliplatin (FOLFOX)) to evaluate immunologic and clinical responses.