RETROVIRUS-MEDIATED GENE-TRANSFER OF B7-1 AND MHC CLASS-II CONVERTS APOORLY IMMUNOGENIC NEUROBLASTOMA INTO A HIGHLY IMMUNOGENIC ONE

The T cell co-stimulatory molecule B7-1 was transduced into a poorly i mmunogenic murine neuroblastoma cell line (Neuro-2a, N-2a) alone or in combination with MHC class II genes to test the ability of these gene s to stimulate antitumor immunity. N-2a cells transduced with B7-1 exh ibited reduced tumorigenicity, whereas N-2a cells overexpressing both MHC class II (syngeneic, I-A(k)) and B7-1 totally abrogated tumorigeni city. Rejection of I-A(k)/B7-1 cells was dependent on both CD4(+) and CD8(+) T cells. The ability of both vaccines to induce protection agai nst parental N-2a was temporally dependent on the time of secondary N- 2a challenge. To investigate the immunity generated by N-2a/B7-1 and N -2a/I-A(k)/B7-1 vaccines, we tested the ability of these modified cell s to stimulate in vitro the proliferation of syngeneic splenocytes fro m naive mice. A significant increase in splenocyte proliferation was o bserved with N-2a/I-A(k)/B7-1 cells compared to N-2a cells. We also de termined that vaccination with N-2a/I-A(k)/B7-1 cells was able to gene rate cytotoxic T cell responses to unmodified N-2a cells. The introduc tion of B9-1 and I-A(k) into N-2a was able to convert a pearly immunog enic tumor to a highly immunogenic one; however, mice bearing large es tablished unmodified tumors had little response to vaccination with N- 2a/I-A(k)/B7-1 cells. Our results emphasize the importance of tumor im munogenicity in the treatment of established tumors with MHC class II/ B7-1 tumor cell vaccines.