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

Wen Yu Pan, Chia Hui Lo, Chun Chi Chen, Ping Yi Wu, Steve R. Roffler, Song Kun Shyue, Mi Hua Tao

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)927-937
Number of pages11
JournalMolecular Therapy
Volume20
Issue number5
DOIs
Publication statusPublished - May 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Fingerprint Dive into the research topics of 'Cancer immunotherapy using a membrane-bound interleukin-12 with B7-1 transmembrane and cytoplasmic domains'. Together they form a unique fingerprint.

Cite this