CT-0508

Early clinical studies, including HER2-targeted CT-0508, demonstrate feasible manufacturing, acceptable safety, tumor infiltration, and immune remodeling, though objective efficacy remains limited. Major challenges include maintaining antitumor polarization, persistence, scalable manufacturing, target selection, and safety control. Continued optimization of CAR-M design and exploitation of myeloid plasticity will be critical to realizing their potential as solid tumor immunotherapy platforms.

Early-phase clinical studies (e.g., CT-0508) demonstrate feasibility and TME remodeling with CAR-MΦ...Emerging combinatorial strategies, such as dual-effector regimens (CAR-NK+ CAR-MΦ), cytokine-modulated cross-support, and bispecific or logic-gated CARs, may overcome these barriers and provide more durable, tumor-selective responses. Taken together, CAR-NK and CAR-MΦ platforms are poised to expand the reach of engineered cell therapy into the solid tumor domain.

These findings demonstrate the preliminary safety, tolerability and manufacturing feasibility of CT-0508 for HER2+ tumors. ClinicalTrials.gov registration: NCT04660929 .

P1, N=48, Active, not recruiting, Carisma Therapeutics Inc | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2023 --> Dec 2024

We have previously developed CT-0508, a chimeric antigen receptor macrophage (CAR-M) targeting HER2 which showed efficacy in a variety of pre-clinical models and is currently in a Phase I clinical trial for patients with HER2+ solid tumors. The presented results demonstrate that CT-1119, an autologous human anti-mesothelin CAR-M, can cause phagocytosis, tumor cell killing, and pro-inflammatory cytokine release in response to stimulation with mesothelin. These results show that CAR-M is a feasible approach for the treatment of mesothelin expressing sold tumors via the potential for induction of a systemic anti-tumor response.

P1, N=48, Recruiting, Carisma Therapeutics Inc | N=18 --> 48 | Trial completion date: Feb 2023 --> Dec 2024 | Trial primary completion date: Feb 2022 --> Jul 2023

Moreover, our findings provide rationale for the combination of CAR-M with immune checkpoint inhibitors. The anti-HER2 CAR-M, CT-0508, is under evaluation in a phase I clinical trial for patients with HER2 overexpressing solid tumors.

Our previously developed human chimeric antigen receptor macrophage (CAR-M) platform has shown potent anti-tumor activity in pre-clinical solid tumor models1, and the anti-HER2 CAR-M CT-0508 is currently being evaluated in a Phase I trial... The CAR-mono platform enables an automated, same-day manufacturing process while maintaining the key characteristics of CAR-M therapy. The use of Ad5f35 for human monocyte transduction primes the cells toward M1 macrophage differentiation and produces a cell population phenotypically and functionally similar to our established CAR-M platform. These data provide strong pre-clinical support to advance the CAR-mono platform into clinical testing.1Klichinsky M, et al.

The anti-HER2 CAR-M, CT-0508, is under evaluation in a phase I clinical trial for patients with HER2 overexpressing solid tumors (NCT04660929).1...Nat Biotechnol. 2020;38(8):947-953.

Moreover, our findings provide rationale for the combination of CAR-M with immune checkpoint inhibitors. The anti-HER2 CAR-M, CT-0508, is under evaluation in a phase I clinical trial for patients with HER2 overexpressing solid tumors.

P1, N=18, Recruiting, Carisma Therapeutics Inc | Not yet recruiting --> Recruiting