MURINE NEUROBLASTOMA VACCINES PRODUCED BY RETROVIRAL TRANSFER OF MHC CLASS-II GENES

Malignant tumors express tumor-related antigens, but effective antitum or immunity does not occur in the primary host. One hypothesis is that there is insufficient stimulation of T-cell responses due to ineffect ive antigen presentation. An approach to overcome these deficiencies i s to modify tumor cells to express major histocompatibility complex (M HC) class II genes and thus facilitate the presentation of antigens di rectly by tumor cells. Our experiments with a murine neuroblastoma cel l line (neuro-2a) transduced with DR (xenogeneic), I-Ab (allogeneic), or I-Ak (syngeneic) MHC class II genes support this notion. The relati ve potencies of the modified neuro-aa to induce immunity to unmodified neuro-2a were neuro-2a/DR > neuro-2a/I-Ab > neuro-2a/I-Ak. Modified n euro-2a also could stimulate naive splenocyte proliferation in vitro. The relative magnitude of the proliferative responses seen after stimu lation with modified tumor cells was neuro-2a/DR > neuro-2a/I-Ab > neu ro-2a/I-Ak > unmodified neuro-2a. Hence, the tumor cell-induced spleno cyte proliferative responses observed in vitro correlate with the effe ctiveness of the tumor cell vaccines to induce antitumor immunity in v ivo. These data show that the expression of exogenous MHC class II on tumor cells is a potent stimulus for specific antitumor immunity. Beca use of the correlation of the in vivo and in vitro immune responses to modified tumor cells, the tumor-induced lymphocyte proliferation assa y may be useful in evaluating tumor cell vaccines produced by addition al genetic modifications of tumor cells.