[Significance of priming of hosts with virus in the tumor-specific immunotherapy model utilizing virus-reactive helper T cell activity].
A tumor-specific immunotherapy model was established utilizing vaccinia virus (VV) in the consideration of clinical application, in which we assessed the significance of priming of hosts with VV to induce in vivo anti-tumor immunity. C3H/HeN mice were pretreated with cyclophosphamide (Cy) to eliminate non-specific suppressor T cell activity and subsequently inoculated (primed) subcutaneously (s.c.) with 10(7)PFU of VV, leading to augmented induction of VV-reactive helper T (VV-Th) cell activities. Four weeks later, the mice were inoculated intradermally (i.d.) with syngeneic X5563 myeloma cells. Six days after the tumor cell inoculation, 5 X 10(7)PFU of VV was injected into the tumor mass 3 times at 2-day intervals. Seven of 10 mice which had received VV-priming and subsequent VV-injection into the tumor mass exhibited complete tumor regression. On the contrary, mice which had received mere intratumoral VV-injection in the absence of VV-priming failed to exhibit appreciable tumor regression. Mice (regressor mice) whose tumor had completely regressed by the above VV-immunotherapy were shown to have acquired systemic anti-tumor immunity which was confirmed by a challenge with syngeneic tumor cells after the tumor regression. In vitro analysis of these immune mice revealed that potent tumor-specific cytotoxic T lymphocyte (CTL) responses were preferentially induced, but with no detectable anti-tumor antibody responses. Such a potent tumor specific immunity was not observed in mice which had received intratumoral VV-injection in the absence of VV-priming.(ABSTRACT TRUNCATED AT 250 WORDS)
Shimizu
Y
Y
Hasumi
K
K
Masubuchi
K
K
Okudaira
Y
Y
D000818:Animals; D005260:Female; D007167:Immunotherapy; D051379:Mice; D008809:Mice, Inbred C3H; D009101:Multiple Myeloma / Q000628:therapy*; D009368:Neoplasm Transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*