T-cell Receptors Specific for Both Rac1- and Rac2-Derived Mutated Epitopes

Simple SummaryContent extracted from patent full text and abstract with AI.

This patent discloses novel T-cell receptors (TCRs) and related antigen-binding proteins that specifically recognize mutated peptide fragments derived from the RAC1 and RAC2 genes (specifically RAC2P29L and RAC1P29S neoantigens) when presented by major histocompatibility complex (MHC) molecules, particularly HLA-A2. The invention includes isolated TCRs, genetic constructs encoding them, engineered T cells expressing these TCRs, and pharmaceutical compositions or therapies utilizing these engineered cells for the detection and immunotherapeutic treatment of cancers expressing the RAC1/RAC2 mutations. The TCRs have demonstrated cross-reactivity for both mutations and can be used in adoptive cell therapies to target tumors harboring either mutated RAC1 or RAC2 proteins.

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

• Developing adoptive T-cell therapies for cancer patients whose tumors carry RAC1P29S or RAC2P29L mutations, such as certain melanomas, breast cancers, or other solid tumors.
• Detecting and diagnosing cancers expressing RAC1 or RAC2 neoantigens via TCR-based assays or ABP-based diagnostic kits.
• Production of engineered T cells for personalized immunotherapy targeting tumors with RAC1/RAC2 mutations.
• Pharmaceutical compositions for administration in cancer immunotherapy protocols, e.g., intravenous infusion of TCR-engineered T-cells.
• Research tools for studying tumor immunology, antigen presentation, and T-cell responses to RAC1/RAC2 neoantigens.
• Screening or monitoring patients for the presence of RAC1/RAC2 mutations as predictive biomarkers for eligibility in T-cell therapy.

BenefitsContent extracted from patent full text and abstract with AI.

• Enables highly specific targeting of tumor cells expressing RAC1/RAC2 neoantigens, minimizing off-target effects and reducing toxicity.
• Covers both RAC1P29S and RAC2P29L mutations with a single engineered receptor, broadening patient applicability and increasing therapeutic impact.
• Improves the prospect of successful treatment for patients with metastatic or resistant cancers carrying these mutations, who often have poor prognosis.
• Can be used in autologous or allogeneic cell therapy settings, providing flexibility in clinical protocols.
• Reduced risk of cross-reactivity with non-tumor tissues due to high selectivity of TCRs, which enhances therapy safety.
• Supports diagnostic applications, enabling precise identification of patients who may benefit from this targeted immunotherapy.

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Inventors & Applicants

Patent Abstract

The invention is based on antigen binding proteins (ABPs) such as T-cell receptors (TCR)expressed on T-cells, which have a specificity to bind to MHC presented Rac2 and Rac1 derived neo-epitopes. Hence, such MHC presented peptides are derived from mutated versions of Rac1and Rac2, such as preferably RAC2P29L and/or RAC1P29S. Provided are isolated ABPs as well as genetic constructs expressing the ABPs, recombinant host cells harboring the ABP of the invention and methods for producing such ABPs and host cells. Moreover, provided are medical applications involving the TCR of the invention, for example in context of an adoptive T-cell therapy.