Nanoparticle therapy reprograms tumor immune cells to attack cancer from within

Good news! Cancer is history (soon)!

"In their approach, when a drug is injected directly into a tumor, macrophages already present in the body absorb it, produce CAR ... proteins on their own, and are converted into anticancer immune cells known as "CAR-macrophages." ...

CAR-macrophages, which have recently attracted attention as a next-generation immunotherapy, have the advantage of directly engulfing cancer cells while simultaneously activating surrounding immune cells to amplify anticancer responses ..."

From the abstract (emphasis added):

"Cancer immunotherapy employing chimeric antigen receptor (CAR) technology has achieved significant clinical success in hematologic malignancies, but faces limitations in solid tumors.

Among alternative strategies, CAR-macrophage therapy offers distinct advantages in solid tumor settings. However, current ex vivo approaches are hindered by inefficient gene transfer into macrophages and challenges in maintaining an antitumor macrophage phenotype.

Here, we report an in situ CAR-macrophage therapy via codelivery of mRNA and immunostimulant. By leveraging lipid nanoparticles (LNPs) designed to selectively transfect tumor-associated macrophages, we circumvent extensive ex vivo manipulation and achieve robust CAR expression directly within the tumor microenvironment.
Furthermore, codelivery of a stimulator of interferon genes (STING) agonist amplifies local immune activation, leading to reinforced CAR-macrophage functionality and enhanced antitumor effects in a mouse melanoma model. This in vivo strategy addressed key obstacles of CAR-macrophage therapy in solid tumors by enabling direct cellular targeting, potent immunomodulation, and simplified manufacturing.

Our findings suggest an LNP-enabled approach for CAR-macrophage immunotherapy to overcome the limitations associated with conventional CAR-T cell therapies."

Nanoparticle therapy reprograms tumor immune cells to attack cancer from within

In Situ Chimeric Antigen Receptor Macrophage Therapy via Co-Delivery of mRNA and Immunostimulant (no public access)

Schematic illustration