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.
Activation of 4-1BBL+ B cells with CD40 agonism and IFNγ elicits potent immunity against glioblastoma
- Views Icon Views
- Share Icon Share
- Search Site
Catalina Lee-Chang, Jason Miska, David Hou, Aida Rashidi, Peng Zhang, Rachel A. Burga, Ignacio Jusué-Torres, 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; Activation of 4-1BBL+ B cells with CD40 agonism and IFNγ elicits potent immunity against glioblastoma. J Exp Med 4 January 2021; 218 (1): e20200913. doi: https://doi.org/10.1084/jem.20200913
Download citation file: