Activation of 4-1BBL+ B cells with CD40 agonism and IFNγ elicits potent immunity against glioblastoma

Catalina Lee-Chang*, Jason Miska, David Hou, Aida Rashidi, Peng Zhang, Rachel A. Burga, Ignacio Torres Jusúe, Ting Xiao, Victor A. Arrieta, Daniel Y. Zhang, Aurora Lopez-Rosas, Yu Han, Adam M. Sonabend, Craig M. Horbinski, Roger Stupp, Irina V. Balyasnikova, MacIej S. Lesniak

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Immunotherapy has revolutionized the treatment of many tumors. However, most glioblastoma (GBM) patients have not, so far, benefited from such successes. With the goal of exploring ways to boost anti-GBM immunity, we developed a B cell-based vaccine (BVax) that consists of 4-1BBL+ B cells activated with CD40 agonism and IFNγ stimulation. BVax migrates to key secondary lymphoid organs and is proficient at antigen cross-presentation, which promotes both the survival and the functionality of CD8+ T cells. A combination of radiation, BVax, and PD-L1 blockade conferred tumor eradication in 80% of treated tumor-bearing animals. This treatment elicited immunological memory that prevented the growth of new tumors upon subsequent reinjection in cured mice. GBM patient-derived BVax was successful in activating autologous CD8+ T cells; these T cells showed a strong ability to kill autologous glioma cells. Our study provides an efficient alternative to current immunotherapeutic approaches that can be readily translated to the clinic.

Original languageEnglish (US)
JournalJournal of Experimental Medicine
Volume218
Issue number1
DOIs
StatePublished - Jan 4 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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