Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes-Reference-Cited by-同舟云学术

Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes

Published:2018-03-02 Issue:6379 Volume:359 Page:1037-1042
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Sockolosky Jonathan T.¹²^ORCID,Trotta Eleonora³,Parisi Giulia⁴^ORCID,Picton Lora¹^ORCID,Su Leon L.¹^ORCID,Le Alan C.⁵,Chhabra Akanksha⁵^ORCID,Silveria Stephanie L.³^ORCID,George Benson M.²⁵⁶^ORCID,King Indigo C.⁷,Tiffany Matthew R.⁸,Jude Kevin¹^ORCID,Sibener Leah V.¹⁹^ORCID,Baker David⁷^ORCID,Shizuru Judith A.⁵^ORCID,Ribas Antoni⁴¹⁰^ORCID,Bluestone Jeffrey A.³¹⁰,Garcia K. Christopher¹²¹⁰¹¹^ORCID

Affiliation:

1. Departments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

2. Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.

3. Diabetes Center and Department of Medicine, University of California, San Francisco, CA 94143, USA.

4. Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA.

5. Department of Blood and Marrow Transplantation, Institute for Stem Cell Biology and Regenerative Medicine, and Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

6. Stanford Medical Scientist Training Program, Stanford University, Stanford, CA 94305, USA.

7. Department of Biochemistry, Howard Hughes Medical Institute, and Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.

8. Department of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.

9. Immunology Graduate Program, Stanford University School of Medicine, Stanford, CA 94305, USA.

10. Parker Institute for Cancer Immunotherapy, 1 Letterman Drive, Suite D3500, San Francisco, CA 94129, USA.

11. Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.

Abstract

Engineering cytokine-receptor pairs Interleukin-2 (IL-2) is an important cytokine that helps T cells destroy tumors and virus-infected cells. IL-2 has great therapeutic promise but is limited by toxic side effects and its capacity to both activate and repress immune responses. Sockolosky et al. set out to improve IL-2–based immunotherapy by engineering synthetic IL-2–receptor pairs (i.e., IL-2 and its receptor, IL-2R) (see the Perspective by Mackall). Engineered complexes transmitted IL-2 signals but only interacted with each other and not with endogenous IL-2/IL-2R. Treatment of mice with IL-2 improved the ability of engineered T cells to reject tumors with no obvious side effects. This type of approach may provide a way to mitigate toxicities associated with some cytokine-based immunotherapies. Science , this issue p. 1037 ; see also p. 990

Funder

Howard Hughes Medical Institute

NIH Office of the Director

Pharmaceutical Research and Manufacturers of America Foundation

Stanford Cancer Institute

Sean N. Parker Autoimmunity Research Laboratory

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference35 articles.

1. Adoptive T Cell Transfer for Cancer Immunotherapy in the Era of Synthetic Biology