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CAR+ and CAR- T cells share a differentiation trajectory into an NK-like subset after CD19 CAR T cell infusion in patients with B cell malignancies.
Louie, Raymond Hall Yip; Cai, Curtis; Samir, Jerome; Singh, Mandeep; Deveson, Ira W; Ferguson, James M; Amos, Timothy G; McGuire, Helen Marie; Gowrishankar, Kavitha; Adikari, Thiruni; Balderas, Robert; Bonomi, Martina; Ruella, Marco; Bishop, David; Gottlieb, David; Blyth, Emily; Micklethwaite, Kenneth; Luciani, Fabio.
Affiliation
  • Louie RHY; School of Computer Science and Engineering, UNSW Sydney, Sydney, NSW, Australia.
  • Cai C; Kirby Institute for Infection and Immunity, UNSW Sydney, Sydney, NSW, Australia.
  • Samir J; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia.
  • Singh M; Kirby Institute for Infection and Immunity, UNSW Sydney, Sydney, NSW, Australia.
  • Deveson IW; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia.
  • Ferguson JM; Kirby Institute for Infection and Immunity, UNSW Sydney, Sydney, NSW, Australia.
  • Amos TG; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia.
  • McGuire HM; Garvan Institute for Medical Research, Sydney, NSW, Australia.
  • Gowrishankar K; Garvan Institute for Medical Research, Sydney, NSW, Australia.
  • Adikari T; Garvan Institute for Medical Research, Sydney, NSW, Australia.
  • Balderas R; Garvan Institute for Medical Research, Sydney, NSW, Australia.
  • Bonomi M; Ramaciotti Facility for Human Systems Biology, The University of Sydney, Sydney, NSW, Australia.
  • Ruella M; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
  • Bishop D; Infection, Immunity and Inflammation Theme, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.
  • Gottlieb D; Blood Transplant and Cell Therapies Program, Department of Haematology, Westmead Hospital, Sydney, NSW, Australia.
  • Blyth E; Westmead Institute for Medical Research, Sydney, NSW, Australia.
  • Micklethwaite K; Kirby Institute for Infection and Immunity, UNSW Sydney, Sydney, NSW, Australia.
  • Luciani F; School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia.
Nat Commun ; 14(1): 7767, 2023 Nov 27.
Article in En | MEDLINE | ID: mdl-38012187
ABSTRACT
Chimeric antigen receptor (CAR) T cell therapy is effective in treating B cell malignancies, but factors influencing the persistence of functional CAR+ T cells, such as product composition, patients' lymphodepletion, and immune reconstitution, are not well understood. To shed light on this issue, here we conduct a single-cell multi-omics analysis of transcriptional, clonal, and phenotypic profiles from pre- to 1-month post-infusion of CAR+ and CAR- T cells from patients from a CARTELL study (ACTRN12617001579381) who received a donor-derived 4-1BB CAR product targeting CD19. Following infusion, CAR+ T cells and CAR- T cells shows similar differentiation profiles with clonally expanded populations across heterogeneous phenotypes, demonstrating clonal lineages and phenotypic plasticity. We validate these findings in 31 patients with large B cell lymphoma treated with CD19 CAR T therapy. For these patients, we identify using longitudinal mass-cytometry data an association between NK-like subsets and clinical outcomes at 6 months with both CAR+ and CAR- T cells. These results suggest that non-CAR-derived signals can provide information about patients' immune recovery and be used as correlate of clinically relevant parameters.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / Lymphoma, Large B-Cell, Diffuse Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2023 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / Lymphoma, Large B-Cell, Diffuse Limits: Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2023 Document type: Article Affiliation country: