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

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 (B-Vax) that consists of 4-1BBL(+) B cells activated with CD40 agonism and IFN gamma 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, B-Vax, 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 B-Vax 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.

Automated summary

The B-Vax vaccine developed in this study showed significant effects in activating autologous CD8(+) T cells and killing GBM cells, achieving an 80% tumor eradication rate in experimental animals.