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

Molecular Therapy : the Journal of the American Society of Gene Therapy
Wen-Yu PanMi-Hua Tao

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 s...Continue Reading

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Citations

Jan 21, 2016·Immunotherapy·Ruben Hernandez-AlcocebaCristian Smerdou
Oct 3, 2015·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Courtney A CohenPaul C Roberts
Jul 18, 2015·PloS One·Chien-Chiao HuangTian-Lu Cheng
Mar 27, 2020·Journal for Immunotherapy of Cancer·Yan GeDavid L Bartlett
Jul 3, 2015·Journal of Leukocyte Biology·Simone BattellaGabriella Palmieri
May 6, 2016·Frontiers in Immunology·Nicholas A Cacalano
Feb 20, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ling ZhangSteven A Rosenberg
Aug 21, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Susannah L HewittNadia Luheshi
Nov 13, 2020·Frontiers in Immunology·Khue G NguyenDavid A Zaharoff
Aug 17, 2021·The Journal of Clinical Investigation·Joshua R VeatchStanley R Riddell
Oct 23, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Andreas HombachHinrich Abken

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