flanvotumab (LY3012215) / Eli Lilly - LARVOL DELTA

A novel SIRPA based FiCAR T cells therapy targeting TYRP1 to treat melanoma patients (AACR 2025) - "A well-known anti-TYRP1 binder flanvotumab's scfv was inserted into FiCAR-structure containing CD28 and CD3zeta intra cellular signaling domain and those CAR T cells were studied for both in vitro and in vivo function. TYRP1 based FiCAR grew normally and good transduction rates with low vector copy numbers were achieved. In addition, upon co-culture of TYRP1 FiCAR T cells with tumor cells expressing TYRP1 a rapid and significant release of pro-inflammatory cytokines was detected."

CAR T-Cell Therapy • Clinical • IO biomarker • Tumor mutational burden • Hematological Malignancies • Melanoma • Oncology • Solid Tumor • SIRPA • TMB • TYRP1

Pyroglutamation of cell surface proteins CD47 and TRP1 by glutaminyl cyclase modulates therapeutic antibody binding. (PubMed, Commun Biol) - "Here, we show that pyroglutamation on CD47 and TRP1 modulates the binding of anti(α)-CD47 magrolimab and αTRP1 TA99 and flanvotumab. Furthermore, the N-terminal glutamine on CD47 is crucial for effective antibody recognition, while pyroglutamation of TRP1 is involved in trafficking to the cell surface. These findings highlight that the pyroglutamation by glutaminyl cyclase can modulate the binding affinity of antibodies with therapeutic potential."

Journal • Oncology

Development of Theranostic Radioimmunoconjugates against Tyrosinase-related protein 1, a melanoma-specific antigen (SNMMI 2025) - "Here, we demonstrate that radioimmunoconjugates of the TYRP1-targeting monoclonal antibody flanvotumab can be leveraged for positron emission tomography (PET) and targeted radiotherapy using Lu-177 in the murine B16-F10 and the patient-derived SK-MEL-30 cell lines in vivo... PET/CT and biodistribution studies with [89Zr][Zr(DFO)]-Fla demonstrated high tumor-accumulation, and excellent tumor-to-background ratios in all models (see Figure 1). Skin uptake remained low following tracer administration and decreased throughout the experimental window (up to 8 days post-injection). Following administration of this imaging agent, tumor-to-muscle ratios 144 h post-injection reached 44.6 in the B16-F10-Luc2 model and 104.6 in the SK-MEL-30 model."

IO biomarker • Melanoma • Oncology • Solid Tumor • Tyrosinase • TYRP1

Development of Theranostic Radioimmunoconjugates against Tyrosinase-related protein 1, a melanoma-specific antigen (SNMMI 2025) - "Here, we demonstrate that radioimmunoconjugates of the TYRP1-targeting monoclonal antibody flanvotumab can be leveraged for positron emission tomography (PET) and targeted radiotherapy using Lu-177 in the murine B16-F10 and the patient-derived SK-MEL-30 cell lines in vivo... PET/CT and biodistribution studies with [89Zr][Zr(DFO)]-Fla demonstrated high tumor-accumulation, and excellent tumor-to-background ratios in all models (see Figure 1). Skin uptake remained low following tracer administration and decreased throughout the experimental window (up to 8 days post-injection). Following administration of this imaging agent, tumor-to-muscle ratios 144 h post-injection reached 44.6 in the B16-F10-Luc2 model and 104.6 in the SK-MEL-30 model."

IO biomarker • Melanoma • Oncology • Solid Tumor • Tyrosinase • TYRP1