ArticleCancer medicine2025
SNAP-Tag-Based Recombinant Photoimmunotherapeutic Agents for the Selective Detection and Killing of Light-Accessible Melanotransferrin-Expressing Melanoma and Triple-Negative Breast Cancer.
Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03769506 (A Phase 3, Randomized, Double-Arm, Open-Label, Controlled Trial of ASP-1929 Photoimmunotherapy Versus Physician's Choice Standard of Care for the Treatment of Locoregional, Recurrent Head and Neck Squamous Cell Carcinoma in Patients Who Have Failed or Progressed On or After at Least Two Lines of Therapy, of Which at Least One Line Must Be Systemic Therapy), which is not on this map. Cited by 1 paper.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 3, Randomized, Double-Arm, Open-Label, Controlled Trial of ASP-1929 Photoimmunotherapy Versus Physician's Choice Standard of Care for the Treatment of Locoregional, Recurrent Head and Neck Squamous Cell Carcinoma in Patients Who Have Failed or Progressed On or After at Least Two Lines of Therapy, of Which at Least One Line Must Be Systemic Therapy
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1 citing paper in PubMed.
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Authors and funding
6 authors.
Funding
Abstract
backgroundMelanoma and triple negative breast cancer (TNBC) represent the most aggressive skin and breast cancer subtypes and are associated with poor diagnostic and limited therapeutic options leading to poor prognosis. Melanotransferrin/p97 (MTf), initially identified as a tumor-associated antigen (TAA) in melanoma, is overexpressed in various solid tumors, including TNBC. Beyond its high differential expression and dreadful tumorigenic impact, MTf is also associated with chemoresistance development, and its inhibition significantly hampers tumor progression, making MTf a promising target for effective targeted therapies. Near-infrared photoimmunotherapy (NIR-PIT) is an approach that combines the precision of antibodies directed against specific TAA with the phototoxic effects of a light-sensitive photosensitizer (IR700), activated by near-infrared (NIR) light irradiation. This study aimed to generate a novel photoimmunoconjugate to specifically destroy MTf-positive melanoma and TNBC cells in vitro following NIR light irradiation.
methodsA single-chain variable fragment (scFv) assembled from anti-MTf antibody L49 was recombinantly fused with the SNAP-tag protein (L49(scFv)-SNAP), capable of irreversible and autocatalytic conjugation to any O(6)-benzylguanine (BG) substrate in a 1:1 stoichiometry. Purified full-length SNAP-tag-based fusion protein (L49(scFv)-SNAP-tag) was either conjugated to a BG-modified fluorescent imaging agent (Alexa 488) to specifically assess its selective binding to MTf-expressing cell lines via confocal imaging and flow cytometry or to a BG-modified light-sensitive photosensitizer (IR700) to evaluate its phototoxic properties using an XTT cell viability assay.
resultsThe selective binding and internalization of L49(scFv)-SNAP-Alexa 488 towards MTf-positive melanoma and TNBC cell lines were successfully demonstrated with MTF expression percentages ranging from 52.8 to 83.1. Once confirmed, dose-dependent phototoxicity of L49(scFv)-SNAP-IR700 was achieved on illuminated MTf-positive cell lines showing IC
conclusionThis study highlights the therapeutic potential of MTf as a promising target for the diagnosis as well as selective and efficient elimination of NIR-light-accessible melanoma and TNBC by NIR-PIT.
trial registrationNCT03769506.
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