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

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 t he growth of s.c. established P815 mastocytoma, but local injections with O K432 into the tumor sites on days 3, 6 and 9 resulted in a moderate antitum or effect. On the other hand, the combination therapy significantly suppres sed tumor growth, and the tumor-bearing mice survived longer than those rec eiving only one of the treatment modalities. The significant infiltration o f CD4(+) or CD8(+) T cells and multiple necrosis in the tumor sites were ob served only when the tumor-bearing mice were treated with the combination t herapy. In addition, a transfer experiment using labeled effector cells rev ealed these infiltrated CD8(+) T cells and CD4(+) T cells to be derived fro m the donor and the host respectively. More importantly, the combination th erapy clearly led to higher expression of the mRNA for Th1-type cytokines a nd CXC3 chemokines in the tumor sites than resulted from each of the treatm ent modalities alone. Collectively, these results indicate that local injec tions with OK432 call help the infiltration of adoptively transferred CD8() T cells into the tumor sites and synergistically induce the local product ion of the Th1-type cytokines and CXC3 chemokines.