BONE-MARROW-DERIVED DENDRITIC CELLS PULSED WITH A TUMOR-SPECIFIC PEPTIDE ELICIT EFFECTIVE ANTITUMOR IMMUNITY AGAINST INTRACRANIAL NEOPLASMS

Although the central nervous system (CNS) is often regarded as an immu nologically privileged site, it is well established that specific CNS immunoreactivity can be generated through peripheral vaccination with CNS antigens, Dendritic cells (DC) are potent antigen presenting cells of hematopoietic origin that have emerged as a promising tool for can cer immunotherapy capable of evoking significant anti-tumor immunity w hen pulsed with tumor-associated peptides. To explore a role for DC-ba sed immunization strategies for the treatment of CNS tumors, we develo ped a brain tumor model using the C3 sarcoma cell line which expresses the tumor-specific, major histocompatibility complex (MHC) class I-re stricted peptide epitope E74(49-57). Syngeneic C57B1/6 mice receiving intravenous (i.v.) injections of bone marrow-derived DCs pulsed with E 7 peptide were effectively protected against a subsequent intracerebra l challenge with C3 tumor cells. More importantly, this systemic immun ization strategy was effective in a therapy model as 67% of animals (1 0 of 15) with established (day 7) intracerebral C3 tumors treated with 3 weekly injections of E7 peptide-pulsed DCs achieved a long-term sur vival (>90 days) while no control animals survived beyond day 41, In v ivo depletion of CD8(+) cells, but not CD4(+) or asialo-GM1(+) cells, abrogated the efficacy of E7 peptide-pulsed DC therapy of established tumors, indicating a pivotal role of specific CD8(+) T-cell responses in mediating the anti-tumor effect. Our findings support the hypothesi s that effective CNS anti-tumor immunoreactivity can be generated with DC-based tumor vaccines. (C) 1998 Wiley-Liss. Inc.