Shakoora Sabree

Beyond Dose: The Impact of Intratumoral Injection Volume and Diluent on In Situ Immunization of Cancer

Cancer immunotherapy can improve patient outcomes however, many patients fail to mount a clinically meaningful anti-tumor immune response. In situ immunization is an immunotherapy strategy with the potential to overcome this limitation by altering the tumor microenvironment (TME) in a manner that allows for the tumor to function as a de-facto vaccine. We have been studying a novel in situ immunization agent known as CMP-001 that consists of a TLR9 agonist encased in a virus-like particle. Preliminary studies in murine models have shown that in situ immunization with CMP-001 enhances T cell infiltration within the tumor and induces a systemic anti-tumor response. A phase I clinical trial of CMP-001 in melanoma is showing promising early results. Nevertheless, mechanistic questions remain concerning how in situ immunization with CMP-001 impacts the TME to ultimately lead to a successful anti-tumor immune response. There is a critical need for such information if CMP-001 and other approaches to in situ immunization are to be optimized clinically.

A pilot study conducted in the A20 B-cell lymphoma murine model found that changing the volume of the succinate-based drug-delivery vehicle of CMP-001, with a fixed dose of drug, significantly impacts immune activation and overall survival. My research tests whether these effects are due to enhanced activation of intratumoral immune cells expressing the succinate receptor, SUCNR1, as a result of diluent choice and/or enhanced drainage of CMP-001 to the draining lymph node as a result of increased volume. These studies will provide preclinical data that may guide drug-delivery practices for a broad range of therapeutics that utilize intratumoral injection.



Manuscript ID: vaccines-1357220
Type of manuscript: Article
Title: Monocytes Exposed to Immune Complexes Reduce pDC Type 1 Interferon Response to Vidutolimod
Authors: Shakoora A Sabree, Caitlin D Lemke-Miltner, Sue E Blackwell, Chaobo Yin, Aaron Bossler, Kareem Ebied, Aliasger K Salem, George J Weiner *

Medical School: University of Iowa (MSTP)
Sabree, Shakoora

2206 MERF
United States

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