Vaccine therapy of colorectal cancer patients with tumor antigens

For the first time two tumor-associated antigens were evaluated as adjuvant therapy in combination with granulocyte colony stimulating factor (GM-CSF) for patients with colorectal cancer. The first study involved immunization with the protein, carcinoembryonic antigen (CEA) during one year. This vaccination regimen induced a strong immunoglobulin 1 (IgG1) and IgG4 and a moderate IgG2 response against CEA. The humoral as well as the T cell responses were protracted up to 36 months. The dose of CEA had no or modest effect on these responses. The anti-CEA IgG titers related significantly to survival. Functional HLA-DR epitopes of CEA could be defined which may serve as components of a vaccination strategy. The other vaccine strategy consisted of the epithelial cell adhesion molecule (Ep-Cam) expressed as a transgene in a viral vector, ALVAC. Patients were immunized over 6 weeks. No anti-Ep-Cam specific humoral response was induced, but eventually Ep-Cam specific type 1 T cells were induced. Both vaccines were well tolerated. GM-CSF augmented the responses. A low incidence of GM-CSF antibodies that did not neutralize the effect of GM-CSF was observed.