PRAME Epitopes are T-Cell Immunovulnerabilities in BRD4::NUTM1 Initiated NUT Carcinoma DOI Open Access
Jeffrey L. Jensen,

Sara K. Peterson,

S. Michael Yu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

NUT carcinoma ("NC") is a rare but highly lethal solid tumor without an effective standard of care. NC caused by bromodomain-containing NUTM1 fusion genes, most commonly BRD4::NUTM1 . recruits p300 to acetylate H3K27 forming "megadomains" with the overexpression encapsulated oncogenes, notably MYC Akin , we hypothesized that transcriptional dysregulation would lead generation cancer specific antigens could be therapeutically actionable. Integrating genomics, immunopeptidomics, and computational biology approaches, identified PRAME as predominantly transcribed HLA Class I-presented cancer/testis antigen in NC. Further, show epitope-specific T-cell receptor ("TCR") x CD3 activator bispecific molecule modeled after brenetafusp has potent mediated activity against PRAME+ Our results often expressed due BRD4::NUTM1, induced are promising TCR targets for forthcoming clinical trials one aggressive tumors afflict humans refractory chemotherapy, checkpoint blockade, targeted therapies. We epitopes TCR-based therapeutics like NC, adding growing momentum addressing challenging malignancies therapeutics.

Language: Английский

PRAME Epitopes are T-Cell Immunovulnerabilities in BRD4::NUTM1 Initiated NUT Carcinoma DOI Open Access
Jeffrey L. Jensen,

Sara K. Peterson,

S. Michael Yu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

NUT carcinoma ("NC") is a rare but highly lethal solid tumor without an effective standard of care. NC caused by bromodomain-containing NUTM1 fusion genes, most commonly BRD4::NUTM1 . recruits p300 to acetylate H3K27 forming "megadomains" with the overexpression encapsulated oncogenes, notably MYC Akin , we hypothesized that transcriptional dysregulation would lead generation cancer specific antigens could be therapeutically actionable. Integrating genomics, immunopeptidomics, and computational biology approaches, identified PRAME as predominantly transcribed HLA Class I-presented cancer/testis antigen in NC. Further, show epitope-specific T-cell receptor ("TCR") x CD3 activator bispecific molecule modeled after brenetafusp has potent mediated activity against PRAME+ Our results often expressed due BRD4::NUTM1, induced are promising TCR targets for forthcoming clinical trials one aggressive tumors afflict humans refractory chemotherapy, checkpoint blockade, targeted therapies. We epitopes TCR-based therapeutics like NC, adding growing momentum addressing challenging malignancies therapeutics.

Language: Английский

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