INDUCTION OF ANTIGEN-SPECIFIC T-CELL AND B-CELL IMMUNITY IN COLON-CARCINOMA PATIENTS BY ANTIIDIOTYPIC ANTIBODY

Polyclonal goat anti-idiotypic Abs directed against anti-human gastroi ntestinal carcinoma mAb GA733 were administered to 13 colon cancer pat ients who had their primary tumor and lymph node metastases removed be fore immunotherapy. Patients received four s.c. doses (0.5 to 8 mg eac h) of alum-precipitated anti-idiotypic Ab. Seven of the 13 patients pr oduced anti-anti-Ids that bound specifically to the GA733 epitope on t umor cells and shared idiotopes with mAb GA733. In four of the seven r esponding patients, anti-id therapy specifically modulated T cell resp onses. In two patients who did not demonstrate GA733 Ag/anti-Id-reacti ve T cells before therapy, anti-Id administration induced CD4(+), MHC class II-dependent T cells that specifically proliferated in culture i n response to stimulation with either anti-Id or GA733 Ag. In two othe r patients who did demonstrate Ag/anti-Id-reactive T cells before ther apy, anti-Id administration transiently induced lymphocytes that suppr essed the proliferative responses of cultured pretherapy lymphocytes t o stimulation with anti-Id or GA733 Ag. Nine of the 13 treated patient s showed no evidence of disease after 39 to 86 mo of observation. Five of these patients developed Ag-specific Ab3 and one had, in addition, a T cell response.