Cancer Therapy: Preclinical Interleukin-7 Mediates Selective Expansion of Tumor-redirected Cytotoxic T Lymphocytes (CTLs) without Enhancement of Regulatory T-cell Inhibition
نویسندگان
چکیده
Purpose:The antitumor activity of chimeric antigen receptor (CAR)–redirectedCTLs shouldbe enhanced if it were possible to increase their proliferation and function after adoptive transfer without concomitantly increasing the proliferation and function of regulatory T cells (Treg). Here, we explored whether the lack of IL-7Ra in Treg can be exploited by the targeted manipulation of the interleukin-7 (IL-7) cytokine–cytokine receptor axis in CAR-engrafted Epstein–Barr Virus–specific CTLs (EBV-CTLs) to selectively augment their growth and antitumor activity even in the presence of Treg. Experimental Design:We generated a bicistronic retroviral vector encoding a GD2-specific CAR and the IL-7Ra subunit, expressed the genes in EBV-CTLs, and assessed their capacity to control tumor growth in the presence of Treg in vitro and in vivo when exposed to either interleukin-2 (IL-2) or IL-7 in a neuroblastoma
منابع مشابه
Interleukin-7 mediates selective expansion of tumor-redirected cytotoxic T lymphocytes (CTLs) without enhancement of regulatory T-cell inhibition.
PURPOSE The antitumor activity of chimeric antigen receptor (CAR)-redirected CTLs should be enhanced if it were possible to increase their proliferation and function after adoptive transfer without concomitantly increasing the proliferation and function of regulatory T cells (Treg). Here, we explored whether the lack of IL-7Rα in Treg can be exploited by the targeted manipulation of the interle...
متن کاملInterleukin-7 mediates selective expansion of tumor-redirected cytotoxic T lymphocytes without enhancement of regulatory T-cell inhibition
The Center for Cell and Gene Therapy has a research collaboration with Celgene and bluebird bio. All authors reviewed the manuscript and approved the final version of the manuscript. Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Adoptive transfer of virus-specific CTLs expressing a CAR represents a promising therapy for patients with cance...
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