COOPERATION BETWEEN STAPHYLOCOCCAL-ENTEROTOXIN-B AND LOW-DOSE MELPHALAN IN THE CURE OF MICE BEARING A LARGE MOPC-315 TUMOR AND EXTENSIVE METASTASES

We have recently demonstrated the importance of V beta 8(+)/CD8(+) cel ls for the curative effectiveness of a suboptimal low dose (0.75 mg/kg ) of melphalan (L-phenylalanine mustard; L-PAM) for mice bearing a lar ge s.c. MOPC-315 tumor and extensive metastases. Here we show that sta phylococcal enterotoxin B (SEB), which is known to selectively stimula te T cells expressing members of the TCR-V beta 8 gene family, substan tially improved the curative effectiveness of the suboptimal dose of L -PAM for mice bearing a large MOPC-315 tumor. Moreover, treatment of m ice with mAb F23.1 (anti-V beta 8) abrogated the in vivo therapeutic e ffect of SEB for low dose L-PAM-treated MOPC-315 tumor bearers (L-PAM TuB mice). Analysis of the effect of SEB on the tumor-infiltrating lym phocytes (TILs) demonstrated that the SEB-mediated therapeutic effect was associated with a significant increase in: 1) the percentage of V beta 8(+) cells among the CD8(+) T cells that accumulated in the s.c. tumor nodules, 2) the total number of V beta 8(+)/CD8(+) cells present per tumor on day 4 after low dose L-PAM therapy, and 3) the ability o f the TILs to lyse MOPC-315 tumor cells in vitro in a short term assay . Furthermore, treatment of mice with mAb F23.1 abolished the ability of SEB to render the TIL population of L-PAM TuB mice more cytotoxic i n vitro for MOPC-315 tumor cells. Thus, the SEB-mediated improvement i n the therapeutic outcome of low dose L-PAM therapy for mice bearing a large MOPC-315 tumor may be due in part to SEB-mediated increase in t he contribution of the V beta 8(+) T cells to tumor eradication throug h enhancement in the magnitude of the anti-MOPC-315 lytic activity exh ibited by the TIL population.