T Cell Receptors for Tumor Specific Proteasome Splice Variants and Uses Thereof

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This patent describes novel T cell receptor (TCR) molecules and related constructs that specifically recognize tumor antigens resulting from proteasome-catalyzed peptide splicing, especially mutated Ras proteins found in many cancers. These TCRs and their derivatives can selectively target and bind to unique tumor-specific antigens, enabling new methods for cancer diagnosis, treatment (including T cell therapy and vaccines), and potentially cancer prevention.

Use CasesContent extracted from patent full text and abstract with AI.

• Adoptive T cell therapy for cancers harboring Ras mutations, particularly those with specific proteasome-spliced antigen forms (e.g., certain pancreatic, colon, lung cancers)
• Development of diagnostic tools for identifying cancers that express these spliced tumor-specific antigens
• Production of cancer vaccines targeting spliced peptide variants found in tumor cells
• Engineering autologous or allogeneic T cells for personalized immunotherapy against tumors with specific Ras mutations
• Use in antibody development, CAR-T cells, or other immune constructs targeting these unique tumor-specific antigens

BenefitsContent extracted from patent full text and abstract with AI.

• Enables highly specific targeting of tumor cells by recognizing neoantigens not found in healthy tissues, reducing off-target effects
• Can be used across a variety of cancers with Ras mutations, covering a large unmet medical need
• Overcomes limitations of current immunotherapies that struggle to effectively distinguish cancerous from healthy cells
• Provides both therapeutic (cell therapy, vaccine) and diagnostic applications
• Supports production of pharmaceutical compositions or cell lines with enhanced anti-tumor immune specificity
• May contribute to improved prognosis and survival in difficult-to-treat cancers, like pancreatic and certain lung cancers
• Customizable platform for new cancer immunotherapies as more tumor-specific spliced antigens are discovered

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Inventors & Applicants

Patent Abstract

The present invention pertains to antigen recognizing constructs against tumor specific proteasome splicing variants. The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for tumor cells carrying antigenic epitopes generated by proteasome peptide splicing of tumor specific antigens. The TCRs of the invention, and antigen binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of proliferative diseases, preferably for the treatment of cancer. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.