PMID- 16817689 OWN - NLM STAT- MEDLINE DCOM- 20060809 LR - 20191026 IS - 1092-0684 (Electronic) IS - 1092-0684 (Linking) VI - 9 IP - 6 DP - 2000 Dec 15 TI - Recombinant adenovirus-transduced dendritic cell immunization in a murine model of central nervous system tumor. PG - e6 AB - OBJECT: Dendritic cells (DCs) are potent antigen-presenting cells that have been shown to play a critical role in the initiation of host immune responses against tumor antigens. In this study, a recombinant adenovirus vector encoding the melanoma-associated antigen, MART-1, was used to transduce murine DCs, which were then tested for their ability to activate cytotoxic T lymphocytes (CTLs) and induce protective immunity against B16 melanoma tumor cells implanted intracranially. METHODS: Genetic modification of murine bone marrow-derived DCs to express MART-1 was achieved through the use of an E1-deficient, recombinant adenovirus vector (AdVMART1). Sixty-two C57BL/6 mice were immunized by subcutaneous injection of AdVMART-1-transduced DCs (23 mice), untransduced DCs (17 mice), or sterile saline (22 mice). Using the B16 murine melanoma, which naturally expresses the MART-1 antigen, all the mice were then challenged intracranially with viable, unmodified syngeneic B16 tumor cells 7 days later. Splenocytes obtained from representative animals in each group were harvested for standard cytotoxicity and enzyme-linked immunospot assays. The remaining mice were followed for survival. Immunization of C57BL/6 mice with DCs transduced with AdVMART1-DC elicited the development of antigenspecific CTL responses. As evidenced by a prolonged survival curve when compared with control-immunized mice harboring intracranial B16 tumors, AdMART1-DC vaccination was able to elicit partial protection against central nervous system (CNS) tumor challenge in vivo. However, this CNS antitumor immunity was weaker than that previously demonstrated against subcutaneous B16 tumors in which the same vaccination strategy was used. CONCLUSIONS: These data suggest that immune responses generated against CNS tumors by DC-based vaccines may be different from those obtained against subcutaneous tumors. FAU - Broder, H AU - Broder H AD - Division of Neurosurgery, University of California at Los Angeles School of Medicine, Los Angeles, California 90095-6901, USA. FAU - Anderson, A AU - Anderson A FAU - Odesa, S K AU - Odesa SK FAU - Kremen, T J AU - Kremen TJ FAU - Liau, L M AU - Liau LM LA - eng GR - CA82666/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20001215 PL - United States TA - Neurosurg Focus JT - Neurosurgical focus JID - 100896471 RN - 0 (Antigens, Neoplasm) RN - 0 (Cytokines) RN - 0 (MART-1 Antigen) RN - 0 (MLANA protein, human) RN - 0 (Mlana protein, mouse) RN - 0 (Neoplasm Proteins) SB - IM MH - Adenoviridae/genetics MH - Animals MH - Antigens, Neoplasm MH - Brain Neoplasms/*immunology/pathology/prevention & control MH - Cells, Cultured MH - Cytokines/metabolism MH - Dendritic Cells/cytology/*immunology/metabolism MH - *Disease Models, Animal MH - Female MH - Humans MH - Immunization MH - MART-1 Antigen MH - Melanoma/*immunology/pathology/prevention & control MH - Mice MH - *Mice, Inbred C57BL MH - Neoplasm Proteins/genetics/immunology MH - Neoplasm Transplantation MH - Spleen/cytology MH - T-Lymphocytes, Cytotoxic/immunology/metabolism MH - Transduction, Genetic MH - Xenograft Model Antitumor Assays EDAT- 2006/07/05 09:00 MHDA- 2006/08/10 09:00 CRDT- 2006/07/05 09:00 PHST- 2006/07/05 09:00 [pubmed] PHST- 2006/08/10 09:00 [medline] PHST- 2006/07/05 09:00 [entrez] AID - 090606 [pii] AID - 10.3171/foc.2000.9.6.7 [doi] PST - epublish SO - Neurosurg Focus. 2000 Dec 15;9(6):e6. doi: 10.3171/foc.2000.9.6.7.