Antibody Opsonization of a TLR9 Agonist–Containing Virus-like Particle Enhances In Situ Immunization

Abstract

The immunologic and therapeutic effects of intratumoral (IT) delivery of a novel virus-like particle as a lymphoma immunotherapy were evaluated in preclinical studies with human cells and a murine model. CMP-001 is a virus-like particle composed of the Qβ bacteriophage capsid protein encapsulating an immunostimulatory CpG-A oligodeoxynucleotide TLR9 agonist. In vitro, CMP-001 induced cytokine production, including IFN-α from plasmacytoid dendritic cells, but only in the presence of anti-Qβ Ab. In vivo, IT CMP-001 treatment of murine A20 lymphoma enhanced survival and reduced growth of both injected and contralateral noninjected tumors in a manner dependent on both the ability of mice to generate anti-Qβ Ab and the presence of T cells. The combination of IT CMP-001 with systemic anti–PD-1 enhanced antitumor responses in both injected and noninjected tumors. IT CMP-001 alone or combined with anti–PD-1 augmented T cell infiltration in tumor-draining lymph nodes. We conclude IT CMP-001 induces a robust antitumor T cell response in an anti-Qβ Ab–dependent manner and results in systemic antitumor T cell effects that are enhanced by anti–PD-1 in a mouse model of B cell lymphoma. Early-phase clinical evaluation of CMP-001 and anti–PD-1 combination therapy in lymphoma will begin shortly, based in part on these results.