Results Release | RocRock Biotechnology CAR-M Treatment for Prostate Cancer Preclinical Data Published

According to the predictions in "The Lancet Commission on prostate cancer: planning for the surge in cases," the number of prostate cancer patients worldwide is expected to increase from 1.4 million cases per year in 2020 to 2.9 million cases per year by 2040. It is estimated that the number of annual deaths from prostate cancer will increase by 85% over the next two decades, from 375,000 in 2020 to nearly 700,000 by 2040. Due to underdiagnosis in low- and middle-income countries and the omission of data collection, the actual numbers are likely to be much higher than recorded. Prostate cancer is one of the most common malignant tumors in the male urogenital system and has a severe impact on men's health and quality of life. Prostate cancer is considered an 'immunological desert,' as its unique tumor microenvironment makes immunotherapy less effective. Although traditional treatments such as surgery, radiotherapy, and androgen deprivation therapy show positive effects in the early stages, the treatment outcomes for advanced and metastatic prostate cancer are often unsatisfactory. Recently, the team of Professor Yin Xiushan from RocRock Biotechnology, in collaboration with Professor Liang Chao's team and Professor Zhang Ke's team from Southern University of Science and Technology, published a research paper titled "PSMA-specific CAR-engineered macrophages for therapy of prostate cancer" on the preprint website bioRixv. The paper described the construction of CAR-M cells targeting prostate cancer by introducing PSMA-specific single-chain variable fragments and costimulatory domains into macrophages, and verified their strong antitumor activity and safety in both in vitro and in vivo experiments, laying a solid preclinical foundation for the advancement of clinical trials.

CAR-M cells are genetically engineered to specifically recognize and kill tumor cells. In this study, researchers constructed PSMA-targeted CAR-M cells, which were transduced with a CAR construct containing PSMA-specific single-chain variable fragments (scFv) and costimulatory domains, achieving a specific attack on prostate cancer cells. In vitro experiments confirmed that CAR-M cells could specifically recognize and kill PSMA-expressing prostate cancer cells, and they exhibited a strong pro-inflammatory phenotype, providing a new approach for the immunotherapy of prostate cancer.

To verify the effect of CAR-M cells in vivo, researchers injected PSMA-targeted CAR-M cells into a xenograft mouse model. The experimental results showed that the tumor volume in the mice treated with CAR-M cells was significantly reduced, and the proportion of cell apoptosis in the tumor tissue was markedly increased. Immunohistochemical analysis revealed that CAR-M cells could effectively infiltrate tumor tissues, and no significant off-target toxicity was observed. These results confirmed the antitumor effects of PSMA-targeted CAR-M cells in vivo and supported their potential as a novel immunotherapy for prostate cancer.

The study found that PSMA-targeted CAR-M cells demonstrated good safety and efficacy in in vivo experiments. Histopathological analysis and biochemical test results showed no significant damage to normal tissues by CAR-M cells, further validating their safety in clinical applications. Moreover, the consistency of antitumor effects in vitro and in vivo indicates that CAR-M cells have a promising future in the treatment of prostate cancer. This research marks the first global CAR-M cell treatment plan for prostate cancer and lays the foundation for the application of CAR-M cells in the treatment of advanced pancreatic cancer. PSMA-targeted CAR-M cells have shown significant antitumor effects and good safety in prostate cancer models. In the future, RocRock Biotechnology will evaluate the safety and efficacy of prostate cancer CAR-M in clinical applications. RocRock Biotechnology is a clinical-stage cell pharmaceutical company focusing on the research of macrophage drug treatment for tumors. In 2023, RocRock Biotechnology, in collaboration with the Affiliated Hospital of Xuzhou Medical University, initiated an Investigator Initiated Trial (IIT) for the RR-M01 pipeline, which has completed the dosing assessment of multiple subjects, confirming that the pioneering pipeline RR-M01 has good drug safety and efficacy, bringing new hope for the treatment of malignant solid tumors, especially recurrent and refractory ovarian cancer. The RR-M01 pipeline is expected to complete the enrollment and dosing of the last patient in October 2024. At the same time, the indications for the RR-M01 pipeline have been further expanded to all solid tumors that are HER2-positive or have low expression, and it obtained ethical approval from the Affiliated Hospital of Xuzhou Medical University in early March 2024, having already completed dosing for 4 subjects, with plans to recruit 20 patients in 2024. Clinical trials targeting pancreatic cancer and small cell lung cancer are also progressing smoothly.

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doi: https://doi.org/10.1101/2024.09.07.611792