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Autoimmune antibodies correlate with immune checkpoint therapy-induced toxicities.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Oct 29; Vol. 116 (44), pp. 22246-22251. Date of Electronic Publication: 2019 Oct 14. - Publication Year :
- 2019
-
Abstract
- Immune checkpoint (IC) therapy provides substantial benefits to cancer patients but can also cause distinctive toxicities termed immune-related adverse events (irAEs). Biomarkers to predict toxicities will be necessary to improve management of patients receiving IC therapy. We relied on serological analysis of recombinant cDNA expression libraries to evaluate plasma samples from patients treated with IC therapy and identified autoantibodies, both in pretreatment and on-treatment samples prior to the development of irAEs, which correlate with the development of immune-related hypophysitis (anti-GNAL and anti-ITM2B autoantibodies) and pneumonitis (anti-CD74 autoantibody). We developed an enzyme-linked immunosorbent assay and tested additional patient samples to confirm our initial findings. Collectively, our data suggest that autoantibodies may correlate with irAEs related to IC therapy, and specific autoantibodies may be detected early for the management of irAEs.<br />Competing Interests: Competing interest statement: J.P.A. has ownership in Jounce, Neon, BioAtla, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak, ImaginAb, Hummingbird, Dragonfly, Lytix, and Tvardi Therapeutics and serves as a consultant for Jounce, Kite Pharma, Neon, Amgen, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak, ImaginAb, Tvardi Therapeutics, Lytix, Hummingbird, and Dragonfly. P.S. has ownership in Jounce, Neon, Constellation, Oncolytics, BioAtla, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak, ImaginAb, Lytix, Hummingbird, and Dragonfly and serves as a consultant for Constellation, Jounce, Kite Pharma, Neon, BioAtla, Pieris Pharmaceuticals, Oncolytics Biotech, Merck, BioMx, Forty-Seven, Polaris, Apricity, Marker Therapeutics, Codiak, ImaginAb, Hummingbird, Lytix, and Dragonfly. J.G. serves as a consultant for ARMO Biosciences, AstraZeneca, CRISPR Therapeutics, Jounce, Nektar, Polaris, Pfizer, and Symphogen. C.G.D. and J.P.A. are coauthors on a 2016 workshop report.
- Subjects :
- Adaptor Proteins, Signal Transducing immunology
Aged
Autoantibodies blood
Autoantibodies toxicity
Autoimmune Hypophysitis diagnosis
Autoimmune Hypophysitis immunology
Biomarkers blood
Female
GTP-Binding Protein alpha Subunits, Gi-Go immunology
Humans
Male
Middle Aged
Neoplasms therapy
Pneumonia immunology
Autoantibodies immunology
Autoimmune Hypophysitis etiology
Immunotherapy adverse effects
Pneumonia etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 116
- Issue :
- 44
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 31611368
- Full Text :
- https://doi.org/10.1073/pnas.1908079116