Novel engineered chimeric engulfment receptors trigger T cell effector functions against SIV-infected CD4+ T cells
Adoptive therapy with genetically engineered T cells offers potential for infectious disease treatment in immunocompromised persons. HIV/simian immunodeficiency virus (SIV)-infected cells express phosphatidylserine (PS) early post infection. We tested whether chimeric engulfment receptor (CER) T cel...
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Published in | Molecular therapy. Methods & clinical development Vol. 28; pp. 1 - 10 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
09.03.2023
American Society of Gene & Cell Therapy Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | Adoptive therapy with genetically engineered T cells offers potential for infectious disease treatment in immunocompromised persons. HIV/simian immunodeficiency virus (SIV)-infected cells express phosphatidylserine (PS) early post infection. We tested whether chimeric engulfment receptor (CER) T cells designed to recognize PS-expressing cells could eliminate SIV-infected cells. Lentiviral CER constructs composed of the extracellular domain of T cell immunoglobulin and mucin domain containing 4 (TIM-4), the PS receptor, and engulfment signaling domains were transduced into primary rhesus macaque (RM) T cells. We measured PS binding and T cell engulfment of RM CD4+ T cells infected with SIV expressing GFP and in vitro, TIM-4 CER CD4+ T cells effectively killed SIV-infected cells, which was dependent on TIM-4 binding to PS. Enhanced killing of SIV-infected CD4+ T cells by CER and chimeric antigen receptor T cell combinations was also observed. This installation of innate immune functions into T cells presents an opportunity to enhance elimination of SIV-infected cells, and studies to evaluate their effect in vivo are warranted.
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Corey and colleagues have characterized chimeric engulfment receptor (CER) T cells aimed at targeting phosphatidylserine expressing cells, including apoptotic cells and SIV/HIV-infected cells. The CER T cells based on the TIM-4 binding protein fused to signaling domains from receptors involved in innate immune responses can eliminate SIV-infected cells. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Outpace Bio, Seattle, WA 98109, USA These authors contributed equally |
ISSN: | 2329-0501 2329-0501 |
DOI: | 10.1016/j.omtm.2022.11.004 |