First human clinical trial of CAR-M cell therapy shows promise for solid tumors
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First human clinical trial of CAR-M cell therapy shows promise for solid tumors
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First human clinical trial of CAR-M cell therapy shows promise for solid tumors.
In August 2017, the FDA approved the launch of Novartis’ CAR-T therapy, marking the beginning of the era of cell therapy.
Since then, the FDA has successively approved four other CAR-T therapies for the treatment of leukemia, various relapsed and refractory lymphomas, and relapsed and refractory multiple myeloma.
The development of cancer immunotherapy represented by CAR-T (chimeric antigen receptor-T cells) has brought hope for a cure for blood cancers such as leukemia.
However, in the field of solid tumor treatment, this promising treatment strategy seems to have not developed smoothly.
CAR-M (Chimeric Antigen Receptor Macrophage) developed by Carisma Therapeutics and the Perelman School of Medicine at the University of Pennsylvania announced preliminary data from a Phase 1 multicenter clinical trial at the Society for Cancer Immunotherapy (SITC) annual meeting.
This is the first CAR-M human clinical trial to treat recurrent or metastatic HER2-positive solid tumors through genetically engineered CAR-M .
This phase 1 clinical trial aims to verify the safety, tolerability and feasibility.
The University of Pennsylvania has always been a research center for cell therapy. Carl June , the “father of CAR-T ” , pioneered CAR-T therapy at the University of Pennsylvania.
The first FDA-approved CAR-T therapy, Kymriah , also completed research at the University of Pennsylvania.
Dr. Saar Gill of the Perelman School of Medicine at the University of Pennsylvania developed the CAR-M platform by genetically engineering human macrophages to express antigen-specific chimeric receptors (such as anti-HER2) that can target cancer cells. specific antigens and penetrate solid tumors, engulfing cancer cells.
Since then , Dr. Saar Gill and others founded Carisma Therapeutics to push CAR-M into clinical research.
Dr. Saar Gill said CAR-T cells are designed to recognize tumor-specific antigens and have been successful in some blood cancers, but so far have had no effect on solid tumors.
In this CAR-M clinical trial for solid tumors, we saw that macrophages infused into patients showed high CAR expression and activity, and were well tolerated.
In addition, preliminary data also show that CAR-M has the ability to alter the solid tumor microenvironment and to alter the composition of myeloid cells and T cells.
The FDA also recently granted Fast Track designation to this CAR-M therapy to accelerate clinical trials of its efficacy and safety in patients with solid tumors.
CAR-M is also an individualized cell therapy that first isolates primary monocytes from the patient’s blood and then modifies them with the desired antigen-specific chimeric receptor (eg, anti-HER2) .
The resulting CAR-M cells are cryopreserved, resuscitated and infused back into the patient when needed.
CAR-M could reach immunologically “cold tumors,” or those that are normally undetectable or unresponsive to the immune system, activating them to help make them more receptive to treatment.
Dr. Kim A. Reiss , the lead investigator of the clinical trial , said that tumor cells alone are difficult to stimulate the T cell activation process, but with macrophages, they can elicit a response by penetrating solid tumors, making contact with tumor cells in different ways. , and can survive in the tumor, which makes CAR-M completely different from CAR-T and has great potential for solid tumors.
Currently, Carisma Therapeutics has 3 CAR-M research pipelines, targeting HER2 (treatment of HER2-positive solid tumors) , Mesothelin (treatment of mesothelin-positive solid tumors) and PSMA (treatment of metastatic castration-resistant prostate cancer) .
Reference :
https://carismatx.com/pipeline/
First human clinical trial of CAR-M cell therapy shows promise for solid tumors
(source:internet, reference only)
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