Highly active CAR T cells that bind to a juxtamembrane region of mesothelin and are not blocked by shed mesothelin

Xiufen Liu; Masanori Onda; Nathan Watson; Raffit Hassan; Mitchell Ho; Tapan K Bera; Junxia Wei; Anirban Chakraborty; Richard Beers; Qi Zhou; Asif Shajahan; Parastoo Azadi; Jingyu Zhan; Di Xia; Ira Pastan

doi:10.1073/pnas.2202439119

Highly active CAR T cells that bind to a juxtamembrane region of mesothelin and are not blocked by shed mesothelin

Proc Natl Acad Sci U S A. 2022 May 10;119(19):e2202439119. doi: 10.1073/pnas.2202439119. Epub 2022 May 5.

Authors

Affiliations

¹ Laboratory of Molecular Biology, National Cancer Institute (NCI), Bethesda, MD 20892-4264.
² Thoracic and GI Malignancies Branch, NCI, Bethesda, MD 20892.
³ Analytical Services and Training, University of Georgia, Athens, GA 30602-4712.
⁴ Laboratory of Cell Biology, NCI, Bethesda, MD 20892-4255.

Abstract

SignificanceMesothelin (MSLN) is a cell-surface protein that is a popular target for antibody-based therapies. We have identified shed MSLN as a major obstacle to successful antibody therapies and prepared a monoclonal antibody that inhibits shedding and makes very active CAR T cells whose activity is not blocked by shed MSLN and merits further preclinical development.

Keywords: antibody; cancer; immunotherapy; ovarian cancer; pancreatic cancer.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

MeSH terms

Antibodies, Monoclonal / metabolism
Cell Line, Tumor
GPI-Linked Proteins / metabolism
Mesothelin
Receptors, Chimeric Antigen*
T-Lymphocytes

Substances

Antibodies, Monoclonal
GPI-Linked Proteins
Receptors, Chimeric Antigen
Mesothelin

Abstract

Publication types

MeSH terms

Substances

Grants and funding