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      Intratumor Adoptive Transfer of IL-12 mRNA Transiently Engineered Antitumor CD8+ T Cells

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          Abstract

          <p class="first" id="d9901211e330">Retroviral gene transfer of interleukin-12 (IL-12) into T cells markedly enhances antitumor efficacy upon adoptive transfer but has clinically shown unacceptable severe side effects. To overcome the toxicity, we engineered tumor-specific CD8+ T cells to transiently express IL-12. Engineered T cells injected intratumorally, but not intravenously, led to complete rejections not only of the injected lesion but also of distant concomitant tumors. Efficacy was further enhanced by co-injection with agonist anti-CD137 mAb or by transient co-expression of CD137 ligand. This treatment induced epitope spreading of the endogenous CD8+ T cell immune response in a manner dependent on cDC1 dendritic cells. Mouse and human tumor-infiltrating T lymphocyte cultures can be transiently IL-12 engineered to attain marked immunotherapeutic effects. </p>

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          Author and article information

          Journal
          Cancer Cell
          Cancer Cell
          Elsevier BV
          15356108
          November 2019
          November 2019
          Article
          10.1016/j.ccell.2019.10.006
          31761658
          c101101c-42ac-4b47-b64f-431ceca153eb
          © 2019

          https://www.elsevier.com/tdm/userlicense/1.0/

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