Novel T Cell Receptors and Immune Therapy Using the Same for the Treatment of Cancer

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This invention discloses novel antigen binding proteins, particularly T cell receptor (TCR)-based molecules, that specifically recognize and bind to antigenic peptides resulting from a common frameshift mutation in the Transforming Growth Factor β Receptor 2 (TGFβR2) gene. Such frameshift variants are prevalent in certain types of cancers, especially colorectal cancers with microsatellite instability. The invention includes the TCR proteins themselves, nucleic acids encoding them, vectors to introduce them into cells, and methods for producing cells expressing these unique TCRs. Pharmaceutical compositions containing these constructs are intended for immune therapy, especially adoptive T cell therapy, to selectively target and destroy cancer cells harboring the TGFβR2 frameshift antigen.

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

• Treatment of colorectal cancer patients whose tumors express the TGFβR2(-1) frameshift mutation (common in microsatellite instability-high cancers).
• Treatment of other cancers exhibiting TGFβR2 frameshift mutations and therefore expressing the specific neoantigen targeted by the described TCRs.
• Development of personalized or 'off-the-shelf' adoptive T cell therapies, where a patient’s T cells are engineered to express the novel TCR and administered back to the patient (TCR-T therapy).
• Potential diagnostic or imaging tools using the antigen binding proteins or labelled versions thereof to identify cancer cells expressing the relevant mutant antigen.
• Research applications in studying immune responses to shared neoantigens in cancer.

BenefitsContent extracted from patent full text and abstract with AI.

• Provides highly specific targeting of cancer cells via recognition of a tumor-exclusive neoantigen derived from a prevalent frameshift mutation, minimizing off-target toxicity to healthy cells.
• Broad applicability to many patients due to the high frequency (~77%) of the TGFβR2(-1) neoantigen in certain cancers, allowing for shared (non-personalized) immunotherapy approaches.
• Improves the efficacy and persistence of adoptively transferred T cells by enabling the selection and engineering of TCRs with high affinity and specificity.
• Reduces the need for individualized, expensive neoantigen discovery and therapy design for each patient, streamlining cancer immunotherapy.
• Potential to induce robust anti-tumor immune responses, including increased interferon gamma production, and possible long-lasting immunity against tumor recurrence.

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Patent Abstract

The present invention pertains to antigen binding proteins (ABP) which bind to Transforming Growth Factor β Receptor 2 (TGFβR2) derived antigenic peptides. The invention in particular provides novel ABPs, such as T cell receptor (TCR) based molecules, which are selective and specific for an antigenic peptide derived from a frameshift variant of TGFβR2. The TCR of the invention, and ABPs derived therefrom, are of use for the treatment of a proliferative disorder, such as a cancer positive for the expression of TGFβR2 frameshift peptide. Further provided are nucleic acids encoding the antigen binding proteins of the invention, vectors comprising these nucleic acids, recombinant cells expressing antigen binding proteins and pharmaceutical compositions comprising the compounds of the invention.