The in vivo cell therapy seed Carisma Therapeutics planted with Moderna in 2022 is starting to sprout.
The biotechs teamed up to develop a method to engineer immune cells called macrophages to target solid tumors. Weekly dosing of the therapy, dubbed CAR-M, shrank lung and liver tumors in mice, Carisma announced in a Nov. 8 release. The results were presented at the Society for Immunotherapy of Cancer meeting in Houston.
In Carisma’s in vivo CAR-M, Moderna’s lipid nanoparticle delivery system is used to shuttle mRNA to macrophages while they’re still in the body, giving them a chimeric antigen receptor—the CAR of CAR-M—that targets glypican-3, a protein commonly expressed by hepatocellular carcinoma liver tumors. Armed with the GPC3 antigen, the macrophages then seek out and destroy cancer cells.
"The data demonstrate our ability to generate anti-GPC3 CAR-M cells directly in vivo using mRNA/LNP technology, leading to significant tumor reduction in translationally relevant preclinical models," Carisma's co-founder and chief scientific officer, Michael Klichinsky, Ph.D., said in the release. "This novel off-the-shelf approach offers a promising new strategy for treating hepatocellular carcinoma, and we are eager to advance it toward clinical development."
Carisma and Moderna first struck their CAR-M pact in January 2022, when the mRNA firm paid Carisma $45 million to develop and commercialize up to a dozen oncology targets. The duo recently expanded the CAR-M collab to two undisclosed autoimmune targets.
Carisma’s CAR-M seeks to address two challenges with conventional cell therapy. The first is that the immune cells used are often T cells, known as CAR-T therapy, which struggle to fight solid tumors. Macrophages, on the other hand, do much better at reaching them.
The other challenge is that many cell therapies are autologous, meaning they require extracting cells from the patient, editing them to go after the right target in the lab and then putting them back into the patient, an expensive and time-consuming process.
And even “off-the-shelf” or allogeneic cell therapies, which use cells from donors rather than patients, still face manufacturing hurdles. MRNA, on the other hand, is much cheaper to produce at scale and easy to administer to patients.