CAR-M Pioneer Secures Over $120M in Funding; iPSC and mRNA Technologies Emerge as Key Enablers for Macrophage Cell Therapy Breakthrough

September 11, 2023 / eMedClub News /--Macrophage therapy, as an emerging cellular therapy, can treat diseases by leveraging the immune regulation and anti-tumor activity of macrophages, showing promising prospects in the treatment of solid tumors. Accompanied byUniversity of PennsylvaniaPreclinical studies of CAR-M conducted byCarisma TherapeuticsThe company has advanced the world's first CAR-M product into Phase I clinical trials and obtained FDA Fast Track designation, marking a revolutionary breakthrough in solid tumor treatment with CAR-M. With its CAR-M technology, Carisma Therapeutics has also gained significant attention from investors, securing a total of $120 million (approximately 850 million RMB) in A+B rounds of financing within three years.

Compared with CAR-T and CAR-NK, CAR-M not only can directly kill tumor cells but also has a strong T-cell stimulation function, thereby achieving a combined anti-tumor effect. It is expected to become a powerful tool for solid tumor treatment. However, the development of CAR-M cell therapy is still in the early research and exploration stage, and many technical points need to be overcome to meet the different clinical needs of patients.

FirstMacrophages are the body's first line of defense against viruses and tumor cells, and these cells can develop resistance to commonly used standard viral vectors.Resulting in the inability of viral vectors to infect macrophages,This characteristic also makes it a challenge to attack cancer by modifying macrophages. Secondly, unlike T cells and NK cells that can be massively cloned and expanded, the differentiation and proliferation ability of macrophages is much lower than that of T cells and NK cells.It hardly proliferates in vitro, and obtaining large quantities is a major challenge.This will bring great challenges to the future industrial development.

Toxic side effects are also a clinical application challenge for macrophage therapy.Once macrophages are overactivated in the body, the interleukin factors they secrete, such as IL-1 and IL-6, may cause a cytokine release syndrome (CRS) reaction. Moreover, due to the migratory characteristics of macrophages in the body, after injection, a large portion of exogenous macrophages will pass through the lungs and remain in the liver, which is not conducive to cancer treatment. In addition, the current exploration of macrophage therapy by researchers is still in its early stages, and the tumor microenvironment in humans is much more complex than in animal models. CAR-M, which has shown excellent results in mouse models, may present new potential risks when entering clinical trials.

Therefore, based on the current clinical development challenges of CAR-M therapy, it is crucial to develop CAR-M therapy through effective strategies.Currently, there are not many companies globally deploying CAR-M therapy, and the companies with relatively faster progress abroad are Carisma Therapeutics and Myeloid.Carisma's first CAR-M product was approved by the FDA to enter clinical trials in July 2020.. The company's main development strategy is to enhance anti-tumor effects and achieve therapeutic effects by modifying bone marrow cells (including monocytes and macrophages) in vitro through a tunable cell therapy platform. Its proprietaryViral and Non-Viral Delivery MethodsCapable of achieving efficient gene insertion, modulating macrophage phenotype to pro-inflammatory or anti-inflammatory, and delivering various payloads, including cytokines and antibodies.

Myeloid is utilizedNon-viral Delivery of mRNATo design peripheral blood mononuclear cells (PBMCs, the precursor of macrophages), patient cells are efficiently and safely engineered through flow electroporation technology to express CAR targeting cancer cells, which can reduce toxicity. Moreover, the manufacturing process only takes a few hours, preliminarily overcoming the core pain points in the current clinical application of CAR-M cell therapy.

And in China, there already isSaiyuan Biotech, Jushi Kangji, Kunshi Biotech, Yuanmai Cell, Meisai Biotech, Kaima BiotechCompanies such as Carisma Therapeutics, Inc. have entered the CAR-M field and made significant progress. Overall, the key challenges in developing macrophage immunotherapy include how to massively expand macrophages, make the infused macrophages resistant to the tumor microenvironment in the body, and maintain their anti-tumor state continuously.

Only by pooling the wisdom of all can we accomplish what is best for all. MedCareer will...October 21, 2023InHeld in ShanghaiUCTD Forum 2023: General Cell Drug Development ForumThis conference will invite over 30 pioneers and leaders from the domestic and international frontline of the general cell drug industry, gathering more than 500 industry experts. Focusing on the latest research trends and advancements, it will deeply explore industry pain points such as clinical regulation, treatment standards, and safety of cell therapy. It aims to provide attendees and the industry with a rich scientific exchange feast.