Project overview

Although non-small cell lung cancer (NSCLC) treatment shows unprecedented improvement with immune checkpoint inhibitors (ICIs), only a minority of NSCLC patients (25%) demonstrate long-term benefit. We hypothesize that therapeutic mRNA vaccination, coupled with co-targeting of antigen-presenting cell (APC) immunosuppressive functions, will sharply increase the number of patients who could benefit from ICIs.

Following the paradigm shift in vaccine development due to the COVID-19 pandemic, in which mRNA vaccines came to the forefront, we predict that these novel, cost-effective, flexible technologies will revolutionize personalized cancer care. Based on the complementary expertise of the consortium, we aim to obtain proof of concept (PoC) for a novel NSCLC mRNA vaccine, through the evaluation of an innovative mRNA + siRNA combination therapy to modulate APC toward restructure of the tumor microenvironment (TME).

For this, we will use our proprietary polymeric nanoparticles (NPs) to selectively deliver therapeutic nucleic acids to myeloid cells.

The program will be structured around six work packages (WP)

WP1

mRNA vaccine NPs PoC

WP1 will establish the components of the vaccine, including the design of the tumor antigens, the polymers and the nanoparticles formulation.

WP2

In vitro mono / combined therapies vaccination

In WP2, we will characterize the particles for each monotherapy alone, or combinations of therapeutic siRNA plus mRNA.

WP3

In vivo Immunotherapeutic tools characterization

WP3 will test the safety and efficacy of nanoparticles using tumor-naïve mice and in vitro models simulating the TME.

WP4

In vivo combined therapeutic efficacy

WP4 will evaluate the most effective nanomedicines in mice lung tumor models.

WP5

Nano-immunotherapy personalization

WP5 will work on the personalization of the therapy, by defining tumor antigens from human biopsies analysis.

WP6

Tech Transfer

WP6 will initiate technology transfer, including analysis of patient CTC genomic alterations, prior to presenting clinical trial protocols to regulatory authorities in order to initiate clinical evaluation.