Your browser doesn't support javascript.
loading
Engineered CD47 protects T cells for enhanced antitumour immunity.
Yamada-Hunter, Sean A; Theruvath, Johanna; McIntosh, Brianna J; Freitas, Katherine A; Lin, Frank; Radosevich, Molly T; Leruste, Amaury; Dhingra, Shaurya; Martinez-Velez, Naiara; Xu, Peng; Huang, Jing; Delaidelli, Alberto; Desai, Moksha H; Good, Zinaida; Polak, Roel; May, Audre; Labanieh, Louai; Bjelajac, Jeremy; Murty, Tara; Ehlinger, Zach; Mount, Christopher W; Chen, Yiyun; Heitzeneder, Sabine; Marjon, Kristopher D; Banuelos, Allison; Khan, Omair; Wasserman, Savannah L; Spiegel, Jay Y; Fernandez-Pol, Sebastian; Kuo, Calvin J; Sorensen, Poul H; Monje, Michelle; Majzner, Robbie G; Weissman, Irving L; Sahaf, Bita; Sotillo, Elena; Cochran, Jennifer R; Mackall, Crystal L.
Afiliación
  • Yamada-Hunter SA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Theruvath J; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
  • McIntosh BJ; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Freitas KA; Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Lin F; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Radosevich MT; Immunology Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Leruste A; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Dhingra S; Masters in Translational Research and Applied Medicine Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Martinez-Velez N; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Xu P; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Huang J; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Delaidelli A; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Desai MH; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Good Z; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Polak R; British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
  • May A; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Labanieh L; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Bjelajac J; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
  • Murty T; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
  • Ehlinger Z; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Mount CW; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
  • Chen Y; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Heitzeneder S; Immunology Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Marjon KD; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Banuelos A; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
  • Khan O; Department of Bioengineering, Stanford University, Stanford, CA, USA.
  • Wasserman SL; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Spiegel JY; Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA, USA.
  • Fernandez-Pol S; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Kuo CJ; Program in Biophysics, Stanford University, Stanford, CA, USA.
  • Sorensen PH; Medical Scientist Training Program, Stanford University, Stanford, CA, USA.
  • Monje M; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Majzner RG; Medical Scientist Training Program, Stanford University, Stanford, CA, USA.
  • Weissman IL; Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA.
  • Sahaf B; Neurosciences Program, Stanford University, Stanford, CA, USA.
  • Sotillo E; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Cochran JR; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Mackall CL; Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA, USA.
Nature ; 630(8016): 457-465, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38750365
ABSTRACT
Adoptively transferred T cells and agents designed to block the CD47-SIRPα axis are promising cancer therapeutics that activate distinct arms of the immune system1,2. Here we administered anti-CD47 antibodies in combination with adoptively transferred T cells with the goal of enhancing antitumour efficacy but observed abrogated therapeutic benefit due to rapid macrophage-mediated clearance of T cells expressing chimeric antigen receptors (CARs) or engineered T cell receptors. Anti-CD47-antibody-mediated CAR T cell clearance was potent and rapid enough to serve as an effective safety switch. To overcome this challenge, we engineered the CD47 variant CD47(Q31P) (47E), which engages SIRPα and provides a 'don't eat me' signal that is not blocked by anti-CD47 antibodies. TCR or CAR T cells expressing 47E are resistant to clearance by macrophages after treatment with anti-CD47 antibodies, and mediate substantial, sustained macrophage recruitment to the tumour microenvironment. Although many of the recruited macrophages manifested an M2-like profile3, the combined therapy synergistically enhanced antitumour efficacy. Our study identifies macrophages as major regulators of T cell persistence and illustrates the fundamental challenge of combining T-cell-directed therapeutics with those designed to activate macrophages. It delivers a therapeutic approach that is capable of simultaneously harnessing the antitumour effects of T cells and macrophages, offering enhanced potency against solid tumours.
Asunto(s)
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos T / Inmunoterapia Adoptiva / Antígeno CD47 / Neoplasias Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos T / Inmunoterapia Adoptiva / Antígeno CD47 / Neoplasias Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos