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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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050122001632 |
| _version_ | 1811207932520431616 |
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| author | Daniel Corey Francoise Haeseleer Joe Hou Lawrence Corey |
| author_facet | Daniel Corey Francoise Haeseleer Joe Hou Lawrence Corey |
| author_sort | Daniel Corey |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T04:13:33Z |
| format | Article |
| id | doaj.art-a8c847a552d94692ba2295d4d52350a4 |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-04-12T04:13:33Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-a8c847a552d94692ba2295d4d52350a42022-12-22T03:48:28ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012023-03-0128110Novel engineered chimeric engulfment receptors trigger T cell effector functions against SIV-infected CD4+ T cellsDaniel Corey0Francoise Haeseleer1Joe Hou2Lawrence Corey3CERo Therapeutics, 201 Haskins Way, Suite 230, San Francisco, CA 94080, USA; Corresponding author Daniel Corey, CERo Therapeutics, 201 Haskins Way, Suite 230, South San Francisco, CA 94080, USA.Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USAVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USADepartment of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USAAdoptive 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.http://www.sciencedirect.com/science/article/pii/S2329050122001632SIVHIVchimeric engulfment receptor (CER)TIM-4phosphatidylserine |
| spellingShingle | Daniel Corey Francoise Haeseleer Joe Hou Lawrence Corey Novel engineered chimeric engulfment receptors trigger T cell effector functions against SIV-infected CD4+ T cells Molecular Therapy: Methods & Clinical Development SIV HIV chimeric engulfment receptor (CER) TIM-4 phosphatidylserine |
| title | Novel engineered chimeric engulfment receptors trigger T cell effector functions against SIV-infected CD4+ T cells |
| title_full | Novel engineered chimeric engulfment receptors trigger T cell effector functions against SIV-infected CD4+ T cells |
| title_fullStr | Novel engineered chimeric engulfment receptors trigger T cell effector functions against SIV-infected CD4+ T cells |
| title_full_unstemmed | Novel engineered chimeric engulfment receptors trigger T cell effector functions against SIV-infected CD4+ T cells |
| title_short | Novel engineered chimeric engulfment receptors trigger T cell effector functions against SIV-infected CD4+ T cells |
| title_sort | novel engineered chimeric engulfment receptors trigger t cell effector functions against siv infected cd4 t cells |
| topic | SIV HIV chimeric engulfment receptor (CER) TIM-4 phosphatidylserine |
| url | http://www.sciencedirect.com/science/article/pii/S2329050122001632 |
| work_keys_str_mv | AT danielcorey novelengineeredchimericengulfmentreceptorstriggertcelleffectorfunctionsagainstsivinfectedcd4tcells AT francoisehaeseleer novelengineeredchimericengulfmentreceptorstriggertcelleffectorfunctionsagainstsivinfectedcd4tcells AT joehou novelengineeredchimericengulfmentreceptorstriggertcelleffectorfunctionsagainstsivinfectedcd4tcells AT lawrencecorey novelengineeredchimericengulfmentreceptorstriggertcelleffectorfunctionsagainstsivinfectedcd4tcells |