Reaction of peripheral-blood lymphocytes to the human chorionic gonadotropin beta sub-unit in patients with productive tumors.

Human chorionic gonadotropin (hCG) and its beta sub-unit (hCG beta) are secreted by trophoblast cells during pregnancy, and by tumoral cells of trophoblastic and non-trophoblastic origin. In contrast to hCG, the free hCG beta sub-unit is consistently undetectable in healthy non-pregnant subjects. With this in mind, we sought to determine whether an immune response to hCG beta can be detected in patients with bladder or germ-cell testis cancers. Peripheral-blood mononuclear cells (PBMC) from 31% of patients with hCG beta-productive bladder cancers and 33% of testis-tumor-bearing patients displayed an hCG beta-specific proliferative response, whereas no patients with non-hCG beta-productive cancers had a proliferative response. PBMC from pregnant women and healthy controls did not elicit significant reactivity. By the use of overlapping synthetic peptides, the immunogenic regions of hCG beta were delineated within the central 20-65 portion. Moreover, in 2 bladder-cancer patients with the HLA DR7, DQ2 haplotype, the T-cell response to hCG beta was focused on the hCG beta (20-47) peptide. Taken together, these results indicate that hCG beta is a tumor-associated antigen capable of inducing a cell-mediated immune response in patients with productive tumors.