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 mela...

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Bibliographic Details
Published in:Pharmaceutics 2024-08, Vol.16 (8), p.1046
Main Authors: Reschke, Robin, Enk, Alexander H, Hassel, Jessica C
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Biomarkers
Cancer therapies
Chemokines
Cytokines
Cytotoxicity
ImmTAC
Immune system
Immunotherapy
Lymphocytes
Medical prognosis
Melanoma
Metastasis
Peptides
Review
T cell receptors
T cell-engaging bispecific antibody
tebentafusp
Tumors
Citations: Items that this one cites
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Summary: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.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics16081046