| First Author | Lemke-Miltner CD | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 5 | Pages | 1386-1394 |
| PubMed ID | 31953355 | Mgi Jnum | J:285617 |
| Mgi Id | MGI:6392186 | Doi | 10.4049/jimmunol.1900742 |
| Citation | Lemke-Miltner CD, et al. (2020) Antibody Opsonization of a TLR9 Agonist-Containing Virus-like Particle Enhances In Situ Immunization. J Immunol 204(5):1386-1394 |
| abstractText | 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 Qbeta bacteriophage capsid protein encapsulating an immunostimulatory CpG-A oligodeoxynucleotide TLR9 agonist. In vitro, CMP-001 induced cytokine production, including IFN-alpha from plasmacytoid dendritic cells, but only in the presence of anti-Qbeta 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-Qbeta 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-Qbeta 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. |
