Pradhan et al. demonstrated that a vaccine strategy using a lysate of the diffuse large B-cell lymphoma A20 cell line adjuvanted with the NKT cell agonist α-GalCer was effective and durable against pre-established B ALL lymphoma in mice. Efficacy was dependent on CD8+ T cells and was associated with increases in NKT and NK cells and decreased granulocytic MDSCs and Tregs. Enhanced germinal center reaction and magnitude of class-switching to a Th1 type humoral response were identified as biomarkers of durable response.

Despite initial remission after successful treatments, B lymphoma patients often encounter relapses and resistance causing high mortality. Thus, there is a need to develop therapies that prevent relapse by providing long-term protection and, ultimately, lead to functional cure. In this study, our goal was to develop a simple, clinically relevant, and easily translatable therapeutic vaccine that provides durable immune protection against aggressive B cell lymphoma and identify critical immune biomarkers that are predictive of long-term survival. In a delayed-treatment, aggressive, murine model of A20 B lymphoma that mimics human diffuse large B cell lymphoma, we show that therapeutic A20 lysate vaccine adjuvanted with an NKT cell agonist, alpha-galactosylceramide (alpha-GalCer), provides long-term immune protection against lethal tumor challenges and the antitumor immunity is primarily CD8 T cell dependent. Using experimental and computational methods, we demonstrate that the initial strength of germinal center reaction and the magnitude of class-switching into a Th1 type humoral response are the best predictors for the long-term immunity of B lymphoma lysate vaccine. Our results not only provide fundamentally insights for successful immunotherapy and long-term protection against B lymphomas, but also present a simple, therapeutic vaccine that can be translated easily due to the facile and inexpensive method of preparation.

Author Info: (1) (2) (3) (4)

Author Info: (1) (2) (3) (4)

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