PMID- 11606395 OWN - NLM STAT- MEDLINE DCOM- 20011204 LR - 20081121 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 61 IP - 20 DP - 2001 Oct 15 TI - Administration of interleukin-12 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines in mouse hepatocellular carcinoma. PG - 7563-7 AB - Dendritic cells (DCs) are potent antigen-presenting cells that are capable of priming systemic antitumor immune response. Here, we evaluated the combined effectiveness of tumor lysate-pulsed DC immunization and interleukin (IL)-12 administration on the induction of antitumor immunity in a mouse hepatocellular carcinoma (HCC) model. Mouse DCs were pulsed with lysate of BNL 1ME A.7R.1 (BNL), a BALB/c-derived HCC cell line, and then injected into syngeneic mice in combination with systemic administration of IL-12. Lymphocytes from mice treated with BNL lysate-pulsed DCs and IL-12 showed stronger cytolytic activity and produced higher amounts of IFN-gamma than those from mice treated with BNL lysate-pulsed DCs alone. Although immunization with BNL lysate-pulsed DCs alone did not lead to complete regression of established tumors, it significantly inhibited tumor growth compared with vehicle injection. Importantly, the combined therapy of BNL lysate-pulsed DCs and IL-12 resulted in tumor rejection or significant inhibition of tumor growth compared with mice treated with BNL lysate-pulsed DCs alone. In vivo lymphocyte depletion experiments demonstrated that this combination was dependent on both CD8+ and CD4+ T cells, but not natural killer cells. These results demonstrated that IL-12 administration enhanced the therapeutic effect of immunization of tumor lysate-pulsed DCs against HCC in mice. This combination of IL-12 and DCs may be useful for suppressing the growth of residual tumor after primary therapy of human HCC. FAU - Tatsumi, T AU - Tatsumi T AD - Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan. FAU - Takehara, T AU - Takehara T FAU - Kanto, T AU - Kanto T FAU - Miyagi, T AU - Miyagi T FAU - Kuzushita, N AU - Kuzushita N FAU - Sugimoto, Y AU - Sugimoto Y FAU - Jinushi, M AU - Jinushi M FAU - Kasahara, A AU - Kasahara A FAU - Sasaki, Y AU - Sasaki Y FAU - Hori, M AU - Hori M FAU - Hayashi, N AU - Hayashi N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (Cancer Vaccines) RN - 0 (Recombinant Proteins) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Cancer Vaccines/*immunology MH - Cytotoxicity, Immunologic MH - Dendritic Cells/*immunology MH - Drug Synergism MH - Female MH - Immunotherapy, Adoptive/*methods MH - Interferon-gamma/biosynthesis MH - Interleukin-12/*pharmacology MH - Killer Cells, Natural/immunology MH - Liver Neoplasms, Experimental/immunology/*therapy MH - Mice MH - Mice, Inbred BALB C MH - Neoplasm Transplantation MH - Recombinant Proteins/pharmacology MH - Tumor Cells, Cultured EDAT- 2001/10/19 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/10/19 10:00 PHST- 2001/10/19 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/10/19 10:00 [entrez] PST - ppublish SO - Cancer Res. 2001 Oct 15;61(20):7563-7.