1. ONP-302 Nanoparticles Inhibit Tumor Growth By Altering Tumor-Associated Macrophages And Cancer-Associated Fibroblasts
- Author
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Laxminarasimha, Donthireddy, Prashanthi, Vonteddu, Tushar, Murthy, Taekyoung, Kwak, Rukiye-Nazan, Eraslan, Joseph R, Podojil, Adam, Elhofy, Michael T, Boyne, John J, Puisis, Filippo, Veglia, Surya S, Singh, Farokh, Dotiwala, Luis J, Montaner, and Dmitry I, Gabrilovich
- Subjects
Oncology - Abstract
In this study, we evaluated the ability of negatively charged bio-degradable nanoparticles, ONP- 302, to inhibit tumor growth. Therapeutic treatment with ONP-302 in vivo resulted in a marked delay in tumor growth in three different syngeneic tumor models in immunocompetent mice. ONP- 302 efficacy persisted with depletion of CD8+ T cells in immunocompetent mice and also was effective in immune deficient mice. Examination of ONP-302 effects on components of the tumor microenvironment (TME) were explored. ONP-302 treatment caused a gene expression shift in TAMs toward the pro-inflammatory M1 type and substantially inhibited the expression of genes associated with the pro-tumorigenic function of CAFs. ONP-302 also induced apoptosis in CAFs in the TME. Together, these data support further development of ONP-302 as a novel first-in- class anti-cancer therapeutic that can be used as a single-agent as well as in combination therapies for the treatment of solid tumors due to its ability to modulate the TME.
- Published
- 2022