CAR-Macrophage Therapy for Renal Cancer Treatment

Nature Cancer: Shandong University Develops In Situ CAR-Macrophage Therapy for Renal Cancer Treatment

Chimeric Antigen Receptor Macrophage (CAR-M) therapy has shown great potential in treating solid tumors. However, the phenotypic reprogramming of CAR-M in the immunosuppressive tumor microenvironment limits its antitumor immune capacity.

On April 29, 2025, Professor Jiang Xinyi, Professor Shi Benkang, and colleagues from Shandong University published a research paper titled An in situ engineered chimeric IL-2 receptor potentiates the tumoricidal activity of proinflammatory CAR macrophages in renal cell carcinoma in Nature Cancer, a journal under the Nature family of journals.

The research developed a novel in situ CAR-M cell therapy that enhances the tumoricidal activity of CAR-M cells using an in situ engineered chimeric IL-2 receptor for the treatment of renal cell carcinoma.

In this latest study, the research team reported an in situ engineered chimeric interleukin (IL)-2 signaling receptor (CSR) used to controllably regulate the pro-inflammatory phenotype of chimeric antigen receptor macrophages (CAR-M), enhancing their sustained antitumor immune ability. 

Specifically, the team developed customized lipid nanoparticles (LNPs) that effectively deliver bicircular RNA into macrophages to generate CAR-M cells with co-stimulatory signaling functions. The intracellular inflammatory signaling pathway of CAR-M can be activated by IL-2 therapeutic agents via the synthesized IL-2 receptor, thereby inducing CAR-M to switch to an antitumor phenotype. In a renal cancer mouse model, the combined treatment of hydrogel-mediated LNPs and IL-2 reshaped the immunosuppressive tumor microenvironment and promoted tumor regression.

Overall, the study demonstrates that the synthesized IL-2 receptor can regulate the pro-inflammatory phenotype of CAR-M cells, which is beneficial for CAR-M cell therapy's antitumor immune treatment. This has broad application prospects in other solid malignant tumors.

It is worth mentioning that Nature Cancer also published a News & Views article titled In vivo macrophage engineering for renal cancer therapy alongside the research article.

The article points out that CAR-macrophage therapy has shown good activity in preclinical models of solid tumors. Professor Jiang Xinyi's team combines CAR technology with lipid nanoparticles (LNPs) to create a platform for in vivo macrophage engineering, generating pro-inflammatory CAR-macrophages with sustained tumor-killing activity, becoming an effective therapy for renal cell carcinoma.