Evidence of a cellular immune response against sialyl-Tn in breast and ovarian cancer patients after high-dose chemotherapy, stem cell rescue, and immunization with theratope STn-KLH cancer vaccine

Seven ovarian and 33 breast high-risk stage II/III and stage IV cancer pati ents received high-dose chemotherapy followed by stem cell rescue. Thirty t o 151 days after stem cell transplantation, the patients received their fir st immunotherapy treatment with Theratope STn-KLH cancer vaccine. Most pati ents developed increasing IgG anti-STn titers to a sustained peak after the fourth or fifth immunizations. Only one patient had elevated CA27.29, (MUC 1 mucin) serum levels at trial entry. Five of the seven patients with preim munotherapy elevated serum CA125 levels demonstrated decreasing: CA125 leve ls during immunotherapy, consistent with an antitumor response. Evidence of STn antigen-specific T-cell proliferation was obtained from 17 of the 27 e valuable patients who received at least three immunotherapy treatments, Ele ven of the 26 patients tested had evidence of an anti-STn TI-I, antigen-spe cific T-cell response as determined by interferon-gamma, but not interleuki n (IL)-4, production. After immunization, lytic activity of peripheral bloo d lymphocytes (PBLs) tested against a lymphokine activated killer (LAK)-sen sitive cell line, a natural killer (NK)sensitive cell Line, and an STn-expr essing cancer cell line (OVCAR) increased significantly. In vitro IL-2 trea tment of the PBLs after vaccination greatly enhanced killing of the STn(+) cancer cell line. Evidence of the development of OVCAR specific killing act ivity, over and above that seen due to LAK or NK killing, is presented. The se studies provide the strongest evidence in humans of the development of a n antitumor T-cell response after immunization with a cancer-associated car bohydrate antigen.