REACTION OF PERIPHERAL-BLOOD LYMPHOCYTES TO THE HUMAN CHORIONIC-GONADOTROPIN BETA-SUBUNIT IN PATIENTS WITH PRODUCTIVE TUMORS

Human chorionic gonadotropin (hCG) and its beta sub-unit (hCG beta) ar e secreted by trophoblast cells during pregnancy, and by tumoral cells of trophoblastic and non-trophoblastic origin. In contrast to hCG, th e free hCG beta sub-unit is consistently undetectable in healthy non-p regnant 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 proli ferative response, whereas no patients with non-hCG beta-productive ca ncers had a proliferative response. PBMC from pregnant women and healt hy controls did not elicit significant reactivity. By the use of overl apping synthetic peptides, the immunogenic regions of hCG beta were de lineated within the central 20-65 portion. Moreover, in 2 bladder-canc er patients with the HLA DR7, DQ2 haplotype, the T-cell response to hC G beta was focused on the hCG beta(20-47) peptide. Taken together, the se results indicate that hCG beta is a tumor-associated antigen capabl e of inducing a cell-mediated immune response in patients with product ive tumors. (C) 1995 Wiley-Liss, Inc.