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.

P2, N=60, Active, not recruiting, UNICANCER | Trial primary completion date: Jan 2026 --> Sep 2026

These findings identify inflammation-induced pyroptosis as a central driver of the pathological changes in PON-induced cardiotoxicity. Notably, our work highlights BMP-7's capacity to inhibit these disease-related alterations. Collectively, these results expand on the current knowledge of the mechanistic framework of PON-induced cardiotoxicity, while also emphasizing BMP-7 as a promising therapeutic candidate with potential translational relevance.

TME gene engineering using LOAd703 inflamed immune cold tumors and was followed by long term stabilized disease in several patients. Further evaluation of LOAd703 together with chemotherapy and/or checkpoint inhibitors is warranted.

P1/2, N=40, Not yet recruiting, Instytut Matki I Dziecka

Collectively, the results propose that treatment with LOAd703 and atezolizumab induce an immune phenotype of ICI resistant patients that has previously been reported associative with ICI responsiveness. These results merits further clinical investigation of supplementary LOAd703 treatment to accomplish ICI sensitivity in ICI resistant MM.

LOAd703 was administered every 2 weeks by ultrasound-guided intratumoral injections, combined with a standard-of-care or immune-conditioning gemcitabine-based chemotherapy regimen. A trend of higher interferon-gamma (IFN-γ) plasma levels in the highest LOAd703 dose cohort was observed. The acceptable toxicity associated with LOAd703 and chemotherapy, combined with signs of clinical benefit in poor prognostic cancer patients, warrant further studies.

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