P32-specific CAR T cells with dual antitumor and antiangiogenic therapeutic potential in gliomas

Nat Commun. 2021 Jun 14;12(1):3615. doi: 10.1038/s41467-021-23817-2.

Abstract

Glioblastoma is considered one of the most aggressive malignancies in adult and pediatric patients. Despite decades of research no curative treatment is available and it thus remains associated with a very dismal prognosis. Although recent pre-clinical and clinical studies have demonstrated the feasibility of chimeric antigen receptors (CAR) T cell immunotherapeutic approach in glioblastoma, tumor heterogeneity and antigen loss remain among one of the most important challenges to be addressed. In this study, we identify p32/gC1qR/HABP/C1qBP to be specifically expressed on the surface of glioma cells, making it a suitable tumor associated antigen for redirected CAR T cell therapy. We generate p32 CAR T cells and find them to recognize and specifically eliminate p32 expressing glioma cells and tumor derived endothelial cells in vitro and to control tumor growth in orthotopic syngeneic and xenograft mouse models. Thus, p32 CAR T cells may serve as a therapeutic option for glioblastoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antigens, Neoplasm / immunology
  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Female
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Glioma / genetics
  • Glioma / immunology*
  • Glioma / metabolism
  • Glioma / therapy*
  • Humans
  • Immunotherapy, Adoptive
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mitochondrial Proteins / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Chimeric Antigen / immunology
  • Serine Endopeptidases / metabolism
  • T-Lymphocytes / immunology*
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • C1QBP protein, human
  • C1qbp protein, mouse
  • Carrier Proteins
  • Mitochondrial Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen
  • Serine Endopeptidases
  • hyaluronan-binding protease, human