Targeting advanced prostate cancer with STEAP1 chimeric antigen receptor T cell and tumor-localized IL-12 immunotherapy.

Autor: Bhatia V; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Kamat NV; Division of Medical Oncology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA., Pariva TE; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Wu LT; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Tsao A; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Sasaki K; Department of Bioengineering, Imperial College London, 86 Wood Lane, London, W12 0BZ, UK., Sun H; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Javier G; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Nutt S; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Coleman I; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Hitchcock L; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Zhang A; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Rudoy D; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Gulati R; Public Health Sciences Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Patel RA; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Roudier MP; Department of Urology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA., True LD; Department of Pathology and Laboratory Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA., Srivastava S; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Morrissey CM; Department of Urology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA., Haffner MC; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA.; Department of Pathology and Laboratory Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.; Clinical Research Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Nelson PS; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA.; Division of Medical Oncology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.; Public Health Sciences Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA.; Department of Urology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.; Department of Pathology and Laboratory Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.; Clinical Research Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Priceman SJ; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA.; Department of Immuno-Oncology, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA., Ishihara J; Department of Bioengineering, Imperial College London, 86 Wood Lane, London, W12 0BZ, UK. j.ishihara@imperial.ac.uk., Lee JK; Human Biology Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA. jklee5@fredhutch.org.; Division of Medical Oncology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA. jklee5@fredhutch.org.; Department of Pathology and Laboratory Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA. jklee5@fredhutch.org.; Clinical Research Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA. jklee5@fredhutch.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Apr 11; Vol. 14 (1), pp. 2041. Date of Electronic Publication: 2023 Apr 11.
DOI: 10.1038/s41467-023-37874-2
Abstrakt: Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is a cell surface antigen for therapeutic targeting in prostate cancer. Here, we report broad expression of STEAP1 relative to prostate-specific membrane antigen (PSMA) in lethal metastatic prostate cancers and the development of a STEAP1-directed chimeric antigen receptor (CAR) T cell therapy. STEAP1 CAR T cells demonstrate reactivity in low antigen density, antitumor activity across metastatic prostate cancer models, and safety in a human STEAP1 knock-in mouse model. STEAP1 antigen escape is a recurrent mechanism of treatment resistance and is associated with diminished tumor antigen processing and presentation. The application of tumor-localized interleukin-12 (IL-12) therapy in the form of a collagen binding domain (CBD)-IL-12 fusion protein combined with STEAP1 CAR T cell therapy enhances antitumor efficacy by remodeling the immunologically cold tumor microenvironment of prostate cancer and combating STEAP1 antigen escape through the engagement of host immunity and epitope spreading.
(© 2023. The Author(s).)
Databáze: MEDLINE
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