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In Vivo Delivery of mRNA Encoding CAR to Macrophages for Solid Tumor Therapy

Technology Overview

In a syngeneic mouse model, intravenous CAR mRNA-LNP (encoding M1-polarizing and TAA-specific CAR) effectively suppresses hepatic tumor metastasis without immune checkpoint blockade.
In a syngeneic mouse model, intravenous CAR mRNA-LNP (encoding M1-polarizing and TAA-specific CAR) effectively suppresses hepatic tumor metastasis without immune checkpoint blockade.

A chimeric antigen receptor macrophage (CAR-M) cell therapy has been developed for solid tumors through the in vivo delivery of lipid nanoparticles (LNPs) encapsulating mRNA encoding a tumor-associated antigen (TAA)-specific CAR. This innovative strategy enables the activation and direct expression of CARs in macrophages within the body, bypassing the need for ex vivo cell engineering.
This unique approach offers an off-the-shelf solution with low manufacturing costs and the potential for repeated dosing, enabling long-term treatment without the logistical and scalability challenges associated with traditional cell therapies. By leveraging mRNA-LNP technology, this strategy provides a highly efficient, scalable, and clinically accessible immunotherapy for solid tumors.

Features & Specifications

Features

  • M1-mRNA: Induces effective M1-polarization of macrophage enhancing its anti-tumor ability.
  • CAR-mRNA: Enables macrophages to express chimeric antigen receptors (CARs), allowing them to recognize and attack tumor cells more effectively.
  • Both mRNAs are encapsulated within lipid nanoparticles (LNPs), protecting the mRNA from degradation and ensuring efficient uptake by macrophages.
  • Infiltrating the tumor microenvironment, CAR-macrophages actively engage in tumor cell phagocytosis, antigen presentation, and inflammatory cytokine release, promoting a robust immune activation against solid tumors.

Specifications

  • Macrophages play a pivotal role in cancer immunity, including tumor infiltration, phagocytosis, antigen presentation, and modulation of adaptive immunity for tumor eradication.
  • Dual Mechanism: Combines macrophage activator (M1 polarization) and tumor-targeting CAR expression, leading to a more comprehensive anti-tumor immune response.
  • In Vivo Delivery: Eliminates the need for ex vivo cell engineering, reducing logistical and manufacturing complexity.

Applications & Benefits

  1. Address the challenges of treating solid tumors in clinical immunotherapy.
  2. Reduce the cost of clinical cancer treatment and provide a highly effective therapeutic strategy.
  3. Develop a new IVT-mRNA–LNP drug.

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