Cancer immunotherapy using a membrane-bound interleukin-12 with B7-1 transmembrane and cytoplasmic domains.

摘要: Interleukin-12 (IL-12) has potent antitumor activity, but its clinical application is limited by severe systemic toxicity, which might be alleviated the use of membrane-anchored IL-12. In present study, a new membrane-bound IL-12 containing murine single-chain and B7-1 transmembrane cytoplasmic domains (scIL-12-B7TM) was constructed efficacy in cancer treatment examined protective mechanism investigated. Surface expression scIL-12-B7TM on colon adenocarcinoma cells significantly inhibited growth subcutaneous tumors, suppressed lung metastasis, resulted local suppression unmodified tumors. Intratumoral injection an adenoviral vector encoding not only complete regression majority also distant, untreated Moreover, mice that had been treated with developed memory responses against subsequent tumor challenge. Immunohistochemical staining vivo depletion lymphocyte subpopulations demonstrated both CD8+ T CD4+ contributed to activity scIL-12-B7TM. Importantly, activities were achieved negligible amounts circulation. Our data demonstrate immunotherapy using advantage minimizing levels without compromising efficacy.