Carisma Therapeutics Announces First-in-Human Dosing of CT-0508, a Pioneering CAR-M Therapy Targeting HER2-Positive Solid Tumors

Recently, Carisma Therapeutics announced that it has initiated a Phase I multicenterClinical Trialcompleted the first patient dosing of its chimeric antigen receptor macrophage (CAR-M) therapy, CT-0508, marking the first time a CAR-M therapy has been used in human studies. This therapy targets HER2-positive solid tumors and holds promise for achieving outcomes that current CAR-T therapies have struggled to attain in solid tumors.

CAR-M therapy is similar to CAR-T therapy but centers on macrophages. It involves extracting macrophages from the patient, introducing chimeric antigen receptors (CARs) into these macrophages via genetic engineering, and ultimately achieving tumor cell killing. As key effector cells of innate immunity, macrophages possess potent phagocytic activity. Among them, tumor-associated macrophages (TAMs) are the most important immune cells residing in the tumor microenvironment (TME), exhibiting a dual role in both killing tumors and promoting tumor growth in malignantTumorplays a crucial role in processes such as onset and progression, invasion and metastasis, immune evasion, and angiogenesis and lymphangiogenesis.

Compared to immune cells such as T cells and NK cells, macrophages may more readily infiltrate tumors within the immunosuppressive microenvironment, therebyTumorImmunotherapy Offers New Opportunities, Attracting Growing Attention from Researchers and Investors in Recent Years

Carisma Therapeutics, a biopharmaceutical company founded by star scientists from the University of Pennsylvania and involving CAR-T pioneer Carl June, has consistently attracted significant attention within the industry. The company has completed multiple rounds of financing, with its $59 million Series B round closed in March bringing its total funding to nearly $121 million. Notably, AbbVie has led or participated in several of these investment rounds. Carisma currently boasts multiple CAR-M pipelines for solid tumors, with CT-0508, targeting human epidermal growth factor receptor 2 (HER2), being the most advanced candidate.

CT-0508 incorporates a series of key features capable of successfully treating solid tumors, including the ability to recruit and infiltrate the solid tumor microenvironment (TME), maintain an anti-tumor phenotype in the presence of immunosuppressive factors, and through the presentation of phagocytosedTumorthe ability of substances to activate adaptive immune responses, etc. This therapy was approved in July 2020FDA"Clinical trial approval granted; the first patient has been dosed."

The clinical trial of CT-0508 is being conducted at the University of Pennsylvania and the University of North Carolina. It plans to enroll 18 patients with recurrent or metastatic HER2-positive solid tumors. One group of patients will receive three infusions of 5 billion cells in a dose-escalation manner, while the other group will receive 5 billion cells in a single day. The primary endpoints of the trial are to evaluate the safety and tolerability of CT-0508, as well as other parameters such as objective response rate, progression-free survival, and cytokine release syndrome. Data collection is expected to be completed by February 2022.

In addition to HER2, Carisma has also developed CAR-M therapies targeting PSMA and mesothelin, both of which are currently in the preclinical stage.

Building on the efficacy of CAR-T therapy in hematologic malignancies, researchers are increasingly diversifying CAR-T targets while also turning their attention to other cell types. This has given rise to a series of novel CAR-based cellular therapies, including CAR-NK, CAR-M, and CAR-Treg cells, all of which hold promise for more effectively combating tumors, particularly solid tumors.TumorOpen new pathways. (Bio ValleyBioon.com）

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