Search: onr:"swepub:oai:research.chalmers.se:5543b647-4b47-4a5e-ad2f-744819ef778d" >
Single-Cell RNA Ana...
Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients
-
- Sarén, Tina (author)
- Uppsala universitet,Uppsala University,Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden
-
- Ramachandran, Mohanraj (author)
- Uppsala universitet,Uppsala University,Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden
-
- Gammelgaºrd, Gustav (author)
- Uppsala universitet,Uppsala University,Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden
-
show more...
-
- Lövgren, Tanja (author)
- Uppsala universitet,Uppsala University,Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden
-
- Mirabello, Claudio, 1984- (author)
- Linköpings universitet,Bioinformatik,Tekniska fakulteten,Linköping University
-
- Björklund, Åsa, 1976 (author)
- Chalmers tekniska högskola,Chalmers University of Technology,Chalmers University of Technology, Sweden
-
- Wikström, Kristina (author)
- Karolinska universitetssjukhuset,Karolinska University Hospital,VECURA, Karolinska University Hospital, Sweden
-
- Hashemi, Jamileh (author)
- Uppsala universitet,Uppsala University,Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden
-
- Freyhult, Eva (author)
- Uppsala universitet,Uppsala University,Uppsala University, Sweden
-
- Ahlström, Håkan (author)
- Uppsala universitet,Radiologi,Uppsala University, Uppsala, Sweden; Antaros Medical AB, Sweden,Antaros Medical AB
-
- Amini, Rose Marie (author)
- Uppsala universitet,Uppsala University,Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden
-
- Hagberg, Hans (author)
- Uppsala universitet,Uppsala University,Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden
-
- Loskog, Angelica (author)
- Uppsala universitet,Uppsala University,Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden; Lokon Pharma AB, Uppsala, Sweden
-
- Enblad, Gunilla (author)
- Uppsala universitet,Uppsala University,Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden
-
- Essand, Magnus (author)
- Uppsala universitet,Uppsala University,Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden
-
show less...
-
(creator_code:org_t)
- American Association for Cancer Research Inc. 2023
- 2023
- English.
-
In: Clinical Cancer Research. - : American Association for Cancer Research Inc.. - 1078-0432 .- 1557-3265. ; 29:20, s. 4139-4152
- Related links:
-
https://research.cha... (primary) (free)
-
show more...
-
https://doi.org/10.1...
-
https://research.cha...
-
https://urn.kb.se/re...
-
https://urn.kb.se/re...
-
show less...
Abstract
Subject headings
Close
- Purpose: Although CD19 chimeric antigen receptor T cells (CAR-T) therapy has shown remarkable success in B-cell malignancies, a substantial fraction of patients do not obtain a long-term clinical response. This could be influenced by the quality of the individual CAR-T infusion product. To shed some light on this, clinical outcome was correlated to characteristics of CAR-T infusion products. Patients and Methods: In this phase II study, patients with B-cell lymphoma (n ¼ 23) or leukemia (n ¼ 1) received one or two infusions of third-generation CD19-directed CAR-Ts (2 × 108/m2). The clinical trial was registered at clinicaltrials. gov: NCT03068416. We investigated the transcriptional profile of individual CD19 CAR-T infusion products using targeted single-cell RNA sequencing and multicolor flow cytometry. Results: Two CAR-T infusions were not better than one in the settings used in this study. As for the CAR-T infusion products, we found that effector-like CD8þCAR-Ts with a high polyfunctionality, high cytotoxic and cytokine production profile, and low dysfunctional signature were associated with clinical response. An extended ex vivo expansion time during CAR-T manufacturing negatively influenced the proportion of effector CD8þCAR-Ts in the infusion product. Conclusions: We identified cell-intrinsic characteristics of effector CD8þCAR-Ts correlating with response that could be used as an indicator for clinical outcome. The results in the study also serve as a guide to CAR-T manufacturing practices.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- CD19 antigen; CD27 antigen; interleukin 2 receptor alpha; antigen expression; Article; B cell lymphoma; CD8+ T lymphocyte; cell subpopulation; chimeric antigen receptor immunotherapy; clinical article; clinical feature; clinical outcome; cohort analysis; controlled study; correlational study; cytokine production; cytotoxicity; disease association; ex vivo study; flow cytometry; gene cluster; genetic transcription; human; human cell; leukemia; phase 2 clinical trial; phenotype; RNA analysis; single cell analysis; treatment indication
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database
- By the author/editor
-
Sarén, Tina
-
Ramachandran, Mo ...
-
Gammelgaºrd, Gus ...
-
Lövgren, Tanja
-
Mirabello, Claud ...
-
Björklund, Åsa, ...
-
show more...
-
Wikström, Kristi ...
-
Hashemi, Jamileh
-
Freyhult, Eva
-
Ahlström, Håkan
-
Amini, Rose Mari ...
-
Hagberg, Hans
-
Loskog, Angelica
-
Enblad, Gunilla
-
Essand, Magnus
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Immunology in th ...
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Hematology
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Cancer and Oncol ...
- Articles in the publication
-
Clinical Cancer ...
- By the university
-
Chalmers University of Technology
-
Uppsala University
-
Linköping University