T Cell-Engaging Bispecific Antibodies Targeting gp100 and PRAME: Expanding Application from Uveal Melanoma to Cutaneous Melanoma.

Uveal melanoma represents a rare and aggressive subtype of melanoma with limited treatment options and poor prognosis, especially in the metastatic setting. Tebentafusp, a bispecific fusion protein, offers a promising therapeutic approach by targeting gp100, an antigen highly expressed in uveal melanoma cells, and redirecting T cell-mediated cytotoxicity towards tumor cells. This review provides an overview of the preclinical and clinical data on tebentafusp in the management of metastatic uveal melanoma. We summarize the mechanism of action, clinical efficacy, safety profile, and ongoing research efforts surrounding this innovative immunotherapy. Preclinical studies have demonstrated the ability of tebentafusp to induce potent and specific anti-tumor immune responses against gp100-expressing uveal melanoma cells. Clinical trials have shown encouraging results, with tebentafusp exhibiting meaningful clinical activity in a subset of patients with metastatic uveal melanoma. Importantly, tebentafusp has also demonstrated a manageable safety profile. By specifically targeting tumor cells expressing gp100, tebentafusp offers a promising therapeutic avenue for individuals with metastatic uveal melanoma, meeting a significant clinical need in this context. Continued clinical trials will provide additional insights into the impact of tebentafusp on treatment-resistant metastatic cutaneous melanoma. Furthermore, we are exploring the potential of T cell engagers directed against the cancer testis antigen PRAME, which could have widespread utility in the treatment of cutaneous melanoma as well as other PRAME-expressing malignancies.