Despite the clinical success of anti-CD20 monoclonal antibodies (mAbs) such as rituximab in the treatment of B-cell lymphoma, therapeutic resistance and relapse remain significant challenges, particularly in tumors with low or heterogeneous CD20 expression resulting from antigen loss or phenotypic shifts. In vivo, CO-005 triggered robust intratumoral PCCD and remodelled the tumor microenvironment, characterized by increased macrophage and neutrophil infiltration, thereby enhancing innate immune activation and supporting a dual-mechanism mode of action that couples direct cancer cell killing with myeloid engagement. These findings position CO-005 as a mechanistically distinct and immunologically active therapeutic with the potential to overcome limitations of both CD20- and CD47-directed therapies and expand treatment options for B-cell lymphoma.

P1/2, N=51, Completed, Lokon Pharma AB | Active, not recruiting --> Completed

The small sample size and single arm design limits effect interpretation but the data shows promise for continued clinical investigation. Study registration: NCT04123470.

These results suggest that BMP-7 might inhibit PON-induced cardiotoxicity. Furthermore, our findings pave the way for future translational studies with BMP-7, which can demonstrate the therapeutic potential of BMP-7 in a clinical setting.

P2, N=60, Active, not recruiting, UNICANCER | Trial primary completion date: Sep 2025 --> Dec 2025

P=N/A, N=80, Completed, Istituto Ortopedico Rizzoli | Trial completion date: Jun 2025 --> Oct 2024 | Trial primary completion date: Jun 2025 --> Oct 2024 | Recruiting --> Completed

These results highlight the importance of TAMs in modulating treatment response. This study provides a preclinical proof of concept for the efficacy of combining mifamurtide with doxorubicin in managing chondrosarcoma, highlighting the potential of immunomodulator and chemotherapy co-treatment in improving treatment outcomes.

In this merged analysis with a risk-adapted strategy for nonmetastatic osteosarcoma, the group with unfavorable prognoses, identified by Pgp expression, performed well when mifamurtide, combined with HDIFO in case of poor response, was administered after surgery.

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.

A validated osteosarcoma TME prognostic gene signature has been identified, regardless of mifamurtide treatment. Importantly, a mifamurtide-related signature was also developed. Tumor-immune interactions possibly implicated in disease progression and treatment response were shown.

P2, N=60, Active, not recruiting, UNICANCER | Trial primary completion date: Mar 2025 --> Sep 2025

The ability of CO-005 to trigger strong PCCD while preserving conventional immune responses provides a novel and promising approach for CD47-targeted cancer therapy. Its favorable safety profile, observed in both in vitro and ex vivo studies, positions CO-005 as a promising candidate with potential therapeutic advantages over existing anti-CD47 treatments.