MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) GENE TRANSDUCTION - AN EFFECTIVE TUMOR VACCINE STRATEGY FOR NON-INTRACRANIAL TUMORS

Recently, there has been renewed interest in the concept of tumor vacc ines using genetically engineered tumor cells expressing a variety of cytokines to increase their immunogenicity. Human MCP-1 (JE) is a pote nt chemoattractant and activator of monocytes and T lymphocytes and th us a good candidate gene for a tumor vaccine. We therefore evaluated t he efficacy of vaccines consisting of irradiated tumor cells transduce d with the murine MCP-1 gene in the syngeneic 9L gliosarcoma brain tum or model. 9L cell lines stably expressing murine MCP-1 (9L-JE) and con trol cell lines expressing neomycin 3' phosphotransferase (9L-Neo) wer e generated by infection with a Moloney murine leukemia retroviral vec tor. Fisher 344 rats were immunized with intradermal injections of 5 x 10(5) or 2 x 10(6) irradiated (5000 cGy) 9L-JE, 9L-Neo, and wild-type 9L (9L-WT) cells. Two weeks later immunized and non-immunized animals were challenged with varyious doses of intradermal (5 x 10(6)-5 x 10( 7)) or intracerebral (2 x 10(4)-5 x 10(5)) 9L-WT cells. Intradermal tu mors grew in all non-immunized animals. No tumors grew in animals immu nized with irradiated 9L-JE or 9L-Neo cells and challenged with inocul a of fewer than 5 x 10(5) 9L-WT cells. With higher inocula up to 10(7) cells, tumors appeared in all the animals, but subsequently regressed in the immunized animals. Tumors in animals immunized with 9L-JE were always smaller than tumors in the other groups. In addition, only the 9L-JE vaccine protected against tumor inocula of 5 x 10(7) cells. Thu s vaccination with MCP-1-expressing cells was able to protect animals against at least a 100-fold larger number of challenge tumor cells tha n vaccination with control cells. In contrast to studies with intrader mal tumors, immunization with 9L-JE and 9L-Neo produced only minimal p rotection against intracerebral tumors. There was no significant diffe rence between the 9L-JE and 9L-Neo vaccines in intracerebral challenge . This study suggests that tumor vaccines expressing cytokine genes su ch as MCP-1 can increase the antitumor response. However, the protecti ve effect of these vaccines appears to be largely limited to intraderm al tumors rather than intracerebral tumors.