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Human anti-PSCA CAR macrophages possess potent antitumor activity against pancreatic cancer.
Shah, Zahir; Tian, Lei; Li, Zhixin; Jin, Lewei; Zhang, Jianying; Li, Zhenlong; Barr, Tasha; Tang, Hejun; Feng, Mingye; Caligiuri, Michael A; Yu, Jianhua.
Afiliação
  • Shah Z; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Tian L; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Li Z; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Jin L; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Zhang J; Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Li Z; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Barr T; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Tang H; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA.
  • Feng M; Department of Immuno-Oncology, City of Hope, Los Angeles, CA 91010, USA.
  • Caligiuri MA; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA; City of Hope Comprehensive Cancer Center, Los Angeles, C
  • Yu J; Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA 91010, USA; Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA 91010, USA; Department of Immuno-Oncology, City of Hope, Los Angeles
Cell Stem Cell ; 31(6): 803-817.e6, 2024 Jun 06.
Article em En | MEDLINE | ID: mdl-38663406
ABSTRACT
Due to the limitations of autologous chimeric antigen receptor (CAR)-T cells, alternative sources of cellular immunotherapy, including CAR macrophages, are emerging for solid tumors. Human induced pluripotent stem cells (iPSCs) offer an unlimited source for immune cell generation. Here, we develop human iPSC-derived CAR macrophages targeting prostate stem cell antigen (PSCA) (CAR-iMacs), which express membrane-bound interleukin (IL)-15 and truncated epidermal growth factor receptor (EGFR) for immune cell activation and a suicide switch, respectively. These allogeneic CAR-iMacs exhibit strong antitumor activity against human pancreatic solid tumors in vitro and in vivo, leading to reduced tumor burden and improved survival in a pancreatic cancer mouse model. CAR-iMacs appear safe and do not exhibit signs of cytokine release syndrome or other in vivo toxicities. We optimized the cryopreservation of CAR-iMac progenitors that remain functional upon thawing, providing an off-the-shelf, allogeneic cell product that can be developed into CAR-iMacs. Overall, our preclinical data strongly support the potential clinical translation of this human iPSC-derived platform for solid tumors, including pancreatic cancer.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Células-Tronco Pluripotentes Induzidas / Proteínas Ligadas por GPI / Macrófagos / Antígenos de Neoplasias Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Células-Tronco Pluripotentes Induzidas / Proteínas Ligadas por GPI / Macrófagos / Antígenos de Neoplasias Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article