Exploring the Mechanisms of the Synergistic Effects of Multiple Innate Immune Pathways for Their Use in Cancer Immunotherapy

Presenter

Tiana Naylor

Campus

UMass Amherst

Sponsor

Prabhani Atukorale, Department of Biomedical Engineering, UMass Amherst

Schedule

Session 5, 3:30 PM - 4:15 PM [Schedule by Time][Poster Grid for Time/Location]

Location

Poster Board A34, Campus Center Auditorium, Row 2 (A21-A40) [Poster Location Map]

Abstract

Harnessing and enhancing the natural capabilities of the immune system has shown significant promise in the field of cancer immunotherapy. Codelivery of two innate immune agonists, cdGMP (STING agonist) and MPLA (TLR4 agonist), via encapsulation within the same lipid nanoparticle has previously been proven to drive a synergistic immune response with respect to the production of inflammatory type I interferons by local immune cells in the tumor microenvironment. Recently, the addition of a third innate immune agonist, CpG (TLR9 agonist), into this nanoparticle formulation has been explored as a way to further boost the inflammatory response produced. Several downstream regulatory factors have been hypothesized to play a significant role in the synergy seen between the TLR4, TLR9, and STING pathways. Through the use of three immortalized knockout macrophage cell lines, we show that multiple downstream regulatory factors, namely IRF3, IRF5, and IRF7, are necessary for this synergistic immune response to occur. We also show that incorporation of the third agonist, CpG, may enhance type I interferon production compared to the previous dual agonist formulation in various antigen presenting cell (APC) lines. This mechanistic data is contributing to ongoing work that is exploring the use of these immuno-nanoparticles in cancer vaccinations.

Keywords

Immunoengineering, Cancer Research, Immunotherapy, Nanoparticles

Research Area

Cancer Studies

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