Publications

Introduction

Recently, lipid nanoparticle (LNP)-based mRNA vaccines have gained widespread attention and offer an attractive modality for personalized cancer therapies. However, inducing an effective anti-tumor response often requires the induction of a T cell response breaking self-tolerance mechanisms, a challenge for current therapies. Providence Therapeutics Holdings Inc. has developed a portfolio of ionizable lipids for the INTENT™ LNP platform. These LNP formulations were carefully screened for their desired end use application. While multiple INTENT™ LNP formulations are capable of inducing expansion of antigen specific T cells, the adjuvant activity of each INTENT™ LNP formulations are distinct. Utilizing an in vivo screening model identifying INTENT™ LNP formulations with adjuvant activity capable of breaking self-tolerance allows the selection of candidates with superior anti-tumor efficacy. In the well characterized mouse syngeneic colorectal cancer (CRC) model expressing model glycoprotein antigens from lymphocytic choriomeningitis virus (LCMV, MC38gp), intramuscular administration of this new INTENT™ LNP formulation as a monotherapy in a therapeutic setting significantly delayed
tumor growth and cleared tumors in 50% of treated mice. The data suggests the applicability of our INTENT™ LNP formulations for the development of effective therapeutic mRNA cancer vaccines for multiple solid tumors.

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