THE CELL-BINDING CARBOXYTERMINAL UNDECAPEPTIDE OF SV40 TUMOR-ANTIGEN PROVIDES PROTECTIVE CELL-DEPENDENT IMMUNITY

This paper describes the use of the synthetic carboxyterminal undecape ptide of large SV40 tumour antigen, lys698-thr708 (KT) to protect Balb /c mice against growth of subcutaneously transplanted tumorigenic SV40 -transformed cells (VLM). The vaccine was prepared by conjugation of K T with 3-(2-pyridyldithio)propionic acid N-hydroxysuccinimide (SPDP). Addition of the SPDP-derivative of KT to syngeneic spleen cells render ed KT covalently linked to free thiol-groups of the cell membranes by the formation of -S-S-CH2-CH2-CO-epsilon-NH-lys698 bonds. Vaccination with KT-conjugated cells was intraperitoneal. Alternatively, KT-conjug ated cells were generated in the peritoneum by injection of PDP-KT ((2 -pyridyldithio)propionic acid-KT). As a control Co-60-irradiated VLM c ells were used. In five experiments all VLM-vaccinated and the majorit y of the PDP-KT-(or KT-spleen cell)-vaccinated mice were protected aga inst tumour growth. However, mice pretreated with saline, unconjugated spleen cells, free KT, KT conjugated to bovine serum albumin, or KT w ith incomplete Freund's adjuvant developed tumours. Treatment of PDP-K T-vaccinated mice with anti-CD4 or anti-CD8 immunoglobulin abolished t umour immunity completely. Thus, covalent binding of the carboxytermin al undecapeptide of SV40 tumour antigen to viable, untransformed cells yielded a vaccine which protects Balb/c mice against SV40 tumours.