Repertoire of allo-restricted peptide-specific t cell receptor sequences and use thereof

Abstract

The present invention is directed to a kit-of-parts or composition containing nucleic acid sequences coding for high-avidity, allo-restricted TCR, wherein the TCR are independently directed against the tyrosinase antigen, the melan-A antigen and the survivin antigen. The invention is further directed to a kit-of-parts or composition containing at least three groups of transgenic lymphocytes transformed with vectors coding for TCR against said antigens. Furthermore, the present invention provides a pharmaceutical composition and its use in the treatment of diseases involving malignant cells expressing said tumor-associated antigens. The invention further relates to a nucleic acid molecule coding for a TCR that recognizes the survivin antigen, a TCR encoded thereby and a T cell expressing said TCR. Further, the invention discloses a vector, a cell and a pharmaceutical composition encoding / containing same and their use in the treatment of diseases involving malignant cells expressing survivin.

Description

FIELD OF THE INVENTION[0001]The present invention is directed to a kit-of-parts or composition containing nucleic acid sequences coding for high-avidity, allo-restricted TCR, wherein the TCR are independently directed against the tyrosinase antigen, the melan-A antigen and the survivin antigen. The invention is further directed to a kit-of-parts or composition containing at least three groups of transgenic lymphocytes transformed with vectors coding for TCR against said antigens. Furthermore, the present invention provides a pharmaceutical composition and its use in the treatment of diseases involving malignant cells expressing said tumor-associated antigens. The invention further relates to a nucleic acid molecule coding for a TCR that recognizes the survivin antigen, a TCR encoded thereby and a T cell expressing said TCR. Further, the invention discloses a vector, a cell and a pharmaceutical composition encoding / containing same and their use in the treatment of diseases involving ...

AI Technical Summary

Benefits of technology

This patent provides a new approach to treating diseases caused by cancer cells that express certain proteins. The approach involves using TCR-based therapy to target tumors and avoid immune selection of tumor cells that lack certain proteins. The invention also includes a repertoire of TCR that can be used to treat melanomas and gliomas, among others. The patent also describes a new TCR that shows high affinity against a specific protein. Finally, the patent provides pharmaceutical compositions for use in adoptive cell therapy to effectively treat diseases caused by malignant cells that express certain proteins.

Problems solved by technology

However, patient-derived T cells may have sub-optimal activity.

Furthermore, T cells with appropriate specificity and function for effective tumor eradication are often not available for patients with rapidly progressing tumors.

Further, available TCR are often of low-avidity.

However, the available prior art documents do not show TCR sequences, which are allo-restricted and specific for the survivin, tyrosinase and melan A antigens.

Immune selection of tumor cells poses a severe problem in TCR-based therapies.

Tumors tend to be genetically unstable and may lose their antigens by mutation.

This instability may lead to the generation of antigen-loss variants which are able to escape the immune response.

Therefore, if tumor cells are attacked by T cells recognizing only one single TAA specificity, this might lead to a reduced or even absent success of therapy due to outgrowth of tumor cells lacking expression of the specific TAA.

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