Interferon-alpha gene therapy in combination with CD80 transduction reduces tumorigenicity and growth of established tumor in poorly immunogenic tumor models

Interferon-alpha (IFN-alpha) or CD80 transduction of tumor cells individual ly reduces tumorigenicity and enhances antitumor responses. Here, we report that the combination of IFN-alpha and CD80 cancer gene therapy in poorly i mmunogenic murine tumor models, the colorectal adenocarcinoma cell line MC3 8, and the methylcholanthrene-induced fibrosarcoma cell line MCA205 reduces tumor growth more efficiently without affecting in vitro growth. Wild-type (WT), neomycin-resistance iNeoJ gene-, or CD80-transduced tumor cells grew progressively in all immunocompetent mice. In contrast, IFN-alpha-transduc ed MC38 or MCA205 cells were rejected in 13 of 15 and seven of 15 mice, res pectively. Synergistic effects were observed when IFN-alpha- and CD80-trans duced tumor cells were mixed and inoculated These admired cells were reject ed by 14 of 15 (MC38) or seven of 15 mice (MCA205), whereas, a mixture of I FN-tu and Neo cells or CD80 and Neo cells led to tumors associated with pro gressive growth. Induction of long-lasting tumor immunity against WT tumor cells was demonstrated by rejection of a subsequent rechallenge in 10 of 13 (MC38) and six of seven (MCA205) tumor-free mice. The therapeutic efficacy with established WT MC38 tumors was shown when mice were treated with a va ccine consisting of repetitive injections of IFN-alpha- and CD80-transduced MC38 cells into the contralateral flank (P < 0.01). This treatment was ass ociated with accumulation of CD4(+), CD8(+) cells and dendritic cells withi n the established tumor, demonstrating induction of antitumor immune respon ses. Combination gene therapy using IFN-alpha and CD80 is an effective immu ne therapy of cancer and could be considered for clinical trials.