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PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial.
Dorff, Tanya B; Blanchard, M Suzette; Adkins, Lauren N; Luebbert, Laura; Leggett, Neena; Shishido, Stephanie N; Macias, Alan; Del Real, Marissa M; Dhapola, Gaurav; Egelston, Colt; Murad, John P; Rosa, Reginaldo; Paul, Jinny; Chaudhry, Ammar; Martirosyan, Hripsime; Gerdts, Ethan; Wagner, Jamie R; Stiller, Tracey; Tilakawardane, Dileshni; Pal, Sumanta; Martinez, Catalina; Reiter, Robert E; Budde, Lihua E; D'Apuzzo, Massimo; Kuhn, Peter; Pachter, Lior; Forman, Stephen J; Priceman, Saul J.
Afiliación
  • Dorff TB; Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA. tdorff@coh.org.
  • Blanchard MS; Department of Computational and Quantitative Medicine, City of Hope, Duarte, CA, USA.
  • Adkins LN; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • Luebbert L; Departments of Mathematics and Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Leggett N; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • Shishido SN; Michelson Center for Convergent Bioscience, Convergent Science Institute in Cancer, University of Southern California, Los Angeles, CA, USA.
  • Macias A; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • Del Real MM; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • Dhapola G; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • Egelston C; Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, USA.
  • Murad JP; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • Rosa R; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • Paul J; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • Chaudhry A; Department of Radiology, City of Hope, Duarte, CA, USA.
  • Martirosyan H; Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
  • Gerdts E; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • Wagner JR; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • Stiller T; Department of Computational and Quantitative Medicine, City of Hope, Duarte, CA, USA.
  • Tilakawardane D; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • Pal S; Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
  • Martinez C; Department of Clinical and Translational Project Development, City of Hope, Duarte, CA, USA.
  • Reiter RE; Department of Urology, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA.
  • Budde LE; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • D'Apuzzo M; Department of Pathology, City of Hope, Duarte, CA, USA.
  • Kuhn P; Michelson Center for Convergent Bioscience, Convergent Science Institute in Cancer, University of Southern California, Los Angeles, CA, USA.
  • Pachter L; Departments of Mathematics and Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Forman SJ; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.
  • Priceman SJ; Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Nat Med ; 30(6): 1636-1644, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38867077
ABSTRACT
Despite recent therapeutic advances, metastatic castration-resistant prostate cancer (mCRPC) remains lethal. Chimeric antigen receptor (CAR) T cell therapies have demonstrated durable remissions in hematological malignancies. We report results from a phase 1, first-in-human study of prostate stem cell antigen (PSCA)-directed CAR T cells in men with mCRPC. The starting dose level (DL) was 100 million (M) CAR T cells without lymphodepletion (LD), followed by incorporation of LD. The primary end points were safety and dose-limiting toxicities (DLTs). No DLTs were observed at DL1, with a DLT of grade 3 cystitis encountered at DL2, resulting in addition of a new cohort using a reduced LD regimen + 100 M CAR T cells (DL3). No DLTs were observed in DL3. Cytokine release syndrome of grade 1 or 2 occurred in 5 of 14 treated patients. Prostate-specific antigen declines (>30%) occurred in 4 of 14 patients, as well as radiographic improvements. Dynamic changes indicating activation of peripheral blood endogenous and CAR T cell subsets, TCR repertoire diversity and changes in the tumor immune microenvironment were observed in a subset of patients. Limited persistence of CAR T cells was observed beyond 28 days post-infusion. These results support future clinical studies to optimize dosing and combination strategies to improve durable therapeutic outcomes. ClinicalTrials.gov identifier NCT03873805 .
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoterapia Adoptiva / Proteínas Ligadas a GPI / Neoplasias de la Próstata Resistentes a la Castración / Antígenos de Neoplasias / Proteínas de Neoplasias Límite: Aged / Humans / Male / Middle aged Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoterapia Adoptiva / Proteínas Ligadas a GPI / Neoplasias de la Próstata Resistentes a la Castración / Antígenos de Neoplasias / Proteínas de Neoplasias Límite: Aged / Humans / Male / Middle aged Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos