Plant Virus Intratumoral Immunotherapy with CPMV and PVX Elicits Durable Antitumor Immunity in a Mouse Model of Diffuse Large B-Cell Lymphoma.

Abstract

Plant viruses are naturally occurring nanoparticles and adjuvants that interact with the mammalian immune system. This property can be harnessed in vaccines and immunotherapy. We have previously demonstrated that intratumoral immunotherapy with cowpea mosaic virus (CPMV) stimulates systemic and durable antitumor immunity in mouse tumor models and canine cancer patients. Here we compared the antitumor efficacy of CPMV with potato virus X (PVX) using a mouse model B-cell lymphoma (A20 and BALB/c mice). Despite their diverse morphologies and physiochemical properties, both plant viruses elicited systemic and long-lasting antitumor immune memory, preventing the recurrence of A20 lymphoma in rechallenge experiments. Data indicate differences in the underlying mechanism: CPMV persists longer in the tumor microenvironment (TME) compared to PVX; CPMV is a potent and multivalent toll-like receptor (TLR) agonist (activating TLRs 2, 4 and 7) while PVX may only weakly engage with TLR7. While CPMV and PVX recruit myeloid cells (neutrophils)─CPMV also recruits macrophages. Data further indicate that antiviral T cells may play a role in antitumor efficacy in the case of CPMV immunotherapy, however this may not be the case for PVX. Regardless of the mechanism of action, both CPMV and PVX elicited a durable antitumor response against a B-cell lymphoma tumor model and thus are intratumoral immunotherapy candidates for clinical development.