Multifunctional nanoparticle potentiates the in situ vaccination effect of radiation therapy and enhances response to immune checkpoint blockade.

PubMed ID: 35999216

Author(s): Zhang Y, Sriramaneni RN, Clark PA, Jagodinsky JC, Ye M, Jin W, Wang Y, Bates A, Kerr CP, Le T, Allawi R, Wang X, Xie R, Havighurst TC, Chakravarty I, Rakhmilevich AL, O’Leary KA, Schuler LA, Sondel PM, Kim K, Gong S, Morris ZS. Multifunctional nanoparticle potentiates the in situ vaccination effect of radiation therapy and enhances response to immune checkpoint blockade. Nat Commun. 2022 Aug 23;13(1):4948. doi: 10.1038/s41467-022-32645-x. PMID 35999216

Journal: Nature Communications, Volume 13, Issue 1, Aug 2022

Radiation therapy (RT) activates an in situ vaccine effect when combined with immune checkpoint blockade (ICB), yet this effect may be limited because RT does not fully optimize tumor antigen presentation or fully overcome suppressive mechanisms in the tumor-immune microenvironment. To overcome this, we develop a multifunctional nanoparticle composed of polylysine, iron oxide, and CpG (PIC) to increase tumor antigen presentation, increase the ratio of M1:M2 tumor-associated macrophages, and enhance stimulation of a type I interferon response in conjunction with RT. In syngeneic immunologically “cold” murine tumor models, the combination of RT, PIC, and ICB significantly improves tumor response and overall survival resulting in cure of many mice and consistent activation of tumor-specific immune memory. Combining RT with PIC to elicit a robust in situ vaccine effect presents a simple and readily translatable strategy to potentiate adaptive anti-tumor immunity and augment response to ICB or potentially other immunotherapies.