Local injections of OK432 can help the infiltration of adoptively transferred CD8+ T cells into the tumor sites and synergistically induce the local production of Th1-type cytokines and CXC3 chemokines.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Cancer Immunol Immunother. 2000 Sep;49(7):361-8. Unique Identifier : AIDSLINE MED/20452091
Tatsugami K; Tamada K; Abe K; Harada M; Nomoto K; Department of Immunology, Medical Institute of Bioregulation,; Kyushu University, Fukuoka, Japan.

Abstract: The effect of local injections with streptococcal preparation OK432 on the antitumor effect induced by adoptive immunotherapy (AIT) was investigated. Draining lymph node cells on day 14 after B7-P815 inoculation were used for AIT after in vitro stimulation. AIT on days 7 and 10 showed no effect on the growth of s.c. established P815 mastocytoma, but local injections with OK432 into the tumor sites on days 3, 6 and 9 resulted in a moderate antitumor effect. On the other hand, the combination therapy significantly suppressed tumor growth, and the tumor-bearing mice survived longer than those receiving only one of the treatment modalities. The significant infiltration of CD4+ or CD8+ T cells and multiple necrosis in the tumor sites were observed only when the tumor-bearing mice were treated with the combination therapy. In addition, a transfer experiment using labeled effector cells revealed these infiltrated CD8+ T cells and CD4 T cells to be derived from the donor and the host respectively. More importantly, the combination therapy clearly led to higher expression of the mRNA for Th1-type cytokines and CXC3 chemokines in the tumor sites than resulted from each of the treatment modalities alone. Collectively, these results indicate that local injections with OK432 can help the infiltration of adoptively transferred CD8+ T cells into the tumor sites and synergistically induce the local production of the Th1-type cytokines and CXC3 chemokines.

Keywords: JOURNAL ARTICLE Animal Antigens, CD80/GENETICS/IMMUNOLOGY Antineoplastic Agents/*PHARMACOLOGY Chemokines, CXC/*BIOSYNTHESIS Combined Modality Therapy Cytokines/*BIOSYNTHESIS Cytotoxicity, Immunologic/IMMUNOLOGY CD8-Positive T-Lymphocytes/*IMMUNOLOGY Female Human Immunotherapy, Adoptive/*METHODS Injections, Intralesional Interferon Type II/BIOSYNTHESIS Interleukin-12/BIOSYNTHESIS Lymph Nodes/IMMUNOLOGY Lymphocytes, Tumor-Infiltrating/*IMMUNOLOGY Mice Mice, Inbred DBA Picibanil/*PHARMACOLOGY Sarcoma, Mast-Cell/IMMUNOLOGY/THERAPY Support, Non-U.S. Gov't Th1 Cells/IMMUNOLOGY/METABOLISM Transfection Tumor Necrosis Factor/BIOSYNTHESIS

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