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Mesothelin-Specific...
Mesothelin-Specific CAR T Cells Target Ovarian Cancer
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- Schoutrop, Esther (author)
- Karolinska Inst, Sweden
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- El-Serafi, Ibrahim (author)
- Karolinska Institutet,Linköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Karolinska Inst, Sweden; Port Said Univ, Egypt
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- Poiret, Thomas (author)
- Karolinska Institutet
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- Zhao, Ying (author)
- Karolinska Institutet
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- Gultekin, Okan (author)
- Karolinska Institutet
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- He, Rui (author)
- Karolinska Institutet
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- Moyano-Galceran, Lidia (author)
- Karolinska Institutet
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- Carlson, Joseph W. (author)
- Karolinska Institutet
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- Lehti, Kaisa (author)
- Karolinska Institutet
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- Hassan, Moustapha (author)
- Karolinska Institutet
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- Magalhaes, Isabelle (author)
- Karolinska Institutet
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- Mattsson, Jonas (author)
- Karolinska Institutet
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(creator_code:org_t)
- AMER ASSOC CANCER RESEARCH, 2021
- 2021
- English.
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In: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 81:11, s. 3022-3035
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- New therapeutic options for patients with ovarian cancer are urgently needed. Therefore, we evaluated the efficacy of two second-generation mesothelin (MSLN)-directed CAR T cells in orthotopic mouse models of ovarian cancer. Treatment with CAR T cells expressing an MSLN CAR construct including the CD28 domain (M28z) significantly prolonged survival, but no persistent tumor control was observed. Despite lower response rates, MSLN-4-1BB (MBBz) CAR T cells induced long-term remission in some SKOV3-bearing mice. Tumor-infiltrating M28z and MBBz CAR T cells upregulated PD-1 and LAG3 in an antigen-dependent manner while MSLN+ tumor cells expressed the corresponding ligands (PD-L1 and HLA-DR), demonstrating that coin-hibitory pathways impede CAR T-cell persistence in the ovarian tumor microenvironment. Furthermore, profiling plasma soluble factors identified a cluster of M28z- and MBBz-treated mice characterized by elevated T-cell secreted factors that had increased survival, higher CD8(+) T-cell tumor infiltration, less exhausted CAR T-cell phenotypes, and increased HLA-DR expression by tumor cells. Altogether, our study demonstrates the therapeutic potential of MSLN-CAR T cells to treat ovarian cancer. Significance: These findings demonstrate that MSLN-directed CAR T cells can provide antitumor immunity against ovarian cancer.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Schoutrop, Esthe ...
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El-Serafi, Ibrah ...
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Poiret, Thomas
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Zhao, Ying
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Gultekin, Okan
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He, Rui
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show more...
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Moyano-Galceran, ...
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Carlson, Joseph ...
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Lehti, Kaisa
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Hassan, Moustaph ...
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Magalhaes, Isabe ...
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Mattsson, Jonas
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Cancer Research
- By the university
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Linköping University
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Karolinska Institutet