Augmentation of antitumor immune responses by multiple intratumoral inoculations of replication-conditional HSV and interleukin-12.
Intratumoral inoculation with a herpes simplex virus (HSV) mutant, G207, as an in situ cancer vaccine has been shown to inhibit tumor growth by inducing tumor-specific immune responses. Here, as a step toward the clinical application of this therapeutic approach, we evaluated different protocols for enhancing the antitumor effect. First, in a bilaterally established tumor model with CT26 colon carcinoma, we demonstrated that multiple intratumoral inoculations with G207 induced a greater antitumor effect on both the inoculated and distant tumors than did 1 or 2 inoculations. Second, to boost this antitumor effect, we developed 2 strategies: multiple in situ cancer vaccines with G207 in combination with systemic administration of recombinant interleukin-12 (rIL-12) (G207/systemic rIL-12) or local administration of rIL-12 (G207/local rIL-12). The antitumor effects in both the inoculated and distant tumors by the combined treatments were significantly greater than by either G207 or rIL-12 treatment alone. G207/systemic rIL-12 and G207/local rIL-12 mediated the complete regression of both the inoculated and distant tumors in 67% and 79% of the animals, respectively. These results indicate that multiple intratumoral inoculations of G207 and systemic or local rIL-12 administration work synergistically to facilitate tumor regression and that this combination of treatments may have potential for treating cancer metastasis.
Iizuka
Yukihiko
Y
Neuroimmunology Research Group, Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
Suzuki
Ayuko
A
Kawakami
Yutaka
Y
Toda
Masahiro
M
D000818:Animals; D019496:Cancer Vaccines / Q000737:chemistry*; D045744:Cell Line, Tumor; D002860:Chromium Radioisotopes / Q000378:metabolism; D003110:Colonic Neoplasms / Q000473:pathology; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018664:Interleukin-12 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000737:chemistry; D018139:Simplexvirus / Q000235:genetics*; D013997:Time Factors
D019496:Cancer Vaccines; D002860:Chromium Radioisotopes; D011994:Recombinant Proteins; D018664:Interleukin-12