PMID- 10395660 OWN - NLM STAT- MEDLINE DCOM- 19990729 LR - 20191210 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 163 IP - 2 DP - 1999 Jul 15 TI - Induction of antitumor immunity with dendritic cells transduced with adenovirus vector-encoding endogenous tumor-associated antigens. PG - 699-707 AB - Dendritic cells (DCs) are professional Ag-presenting cells that are being considered as potential immunotherapeutic agents to promote host immune responses against tumor Ags. In this study, recombinant adenovirus (Ad) vectors encoding melanoma-associated Ags were used to transduce murine DCs, which were then tested for their ability to activate CTL and induce protective immunity against B16 melanoma tumor cells. Immunization of C57BL/6 mice with DCs transduced with Ad vector encoding the hugp100 melanoma Ag (Ad2/hugp100) elicited the development of gp100-specific CTLs capable of lysing syngeneic fibroblasts transduced with Ad2/hugp100, as well as B16 cells expressing endogenous murine gp100. The induction of gp100-specific CTLs was associated with long term protection against lethal s.c. challenge with B16 cells. It was also possible to induce effective immunity against a murine melanoma self Ag, tyrosinase-related protein-2, using DCs transduced with Ad vector encoding the Ag. The level of antitumor protection achieved was dependent on the dose of DCs and required CD4+ T cell activity. Importantly, immunization with Ad vector-transduced DCs was not impaired in mice that had been preimmunized against Ad to mimic the immune status of the general human population. Finally, DC-based immunization also afforded partial protection against established B16 tumor cells, and the inhibition of tumor growth was improved by simultaneous immunization against two melanoma-associated Ags as opposed to either one alone. Taken together, these results support the concept of cancer immunotherapy using DCs transduced with Ad vectors encoding tumor-associated Ags. FAU - Kaplan, J M AU - Kaplan JM AD - Genzyme Corporation, Genzyme Molecular Oncology, Framingham, MA 01701, USA. jkaplan@genzyme.com FAU - Yu, Q AU - Yu Q FAU - Piraino, S T AU - Piraino ST FAU - Pennington, S E AU - Pennington SE FAU - Shankara, S AU - Shankara S FAU - Woodworth, L A AU - Woodworth LA FAU - Roberts, B L AU - Roberts BL LA - eng PT - Journal Article PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antigens, Neoplasm) RN - 0 (Melanoma-Specific Antigens) RN - 0 (Membrane Glycoproteins) RN - 0 (Neoplasm Proteins) RN - 0 (PMEL protein, human) RN - 0 (Pmel protein, mouse) RN - 0 (gp100 Melanoma Antigen) SB - IM MH - Adenoviridae/genetics/*immunology MH - Animals MH - Antigens, Neoplasm/*immunology MH - Bone Marrow Cells/immunology MH - CD4-Positive T-Lymphocytes/immunology MH - Dendritic Cells/immunology/*transplantation/virology MH - Female MH - Genetic Vectors/immunology MH - Humans MH - Immunotherapy, Active MH - Immunotherapy, Adoptive/methods MH - Melanoma, Experimental/*immunology/*therapy MH - Melanoma-Specific Antigens MH - Membrane Glycoproteins/genetics/immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Neoplasm Proteins/genetics/*immunology MH - T-Lymphocytes, Cytotoxic/immunology MH - Transfection/*immunology MH - gp100 Melanoma Antigen EDAT- 1999/07/08 00:00 MHDA- 1999/07/08 00:01 CRDT- 1999/07/08 00:00 PHST- 1999/07/08 00:00 [pubmed] PHST- 1999/07/08 00:01 [medline] PHST- 1999/07/08 00:00 [entrez] AID - ji_v163n2p699 [pii] PST - ppublish SO - J Immunol. 1999 Jul 15;163(2):699-707.