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1. WO2020109616 - MODIFICATION DE LYMPHOCYTES T

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

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Claims:

1. A modified T cell or population of modified T cells comprising a heterologous CD8 co-receptor and a heterologous T cell receptor (TCR).

2. A modified T cell or population of modified T cells according to claim 1 wherein the CD8 co-receptor is CD8a.

3. A modified T cell or population of modified T cells according to claim 2 wherein the CD8 co-receptor comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 1.

4. A modified T cell or population according to modified T cells according to any one of claims 1 to 3 wherein the TCR binds a cancer or tumour antigen or peptide thereof and/or is an affinity enhanced TCR.

5. A modified T cell or population of modified T cells according to any one of claims 1 to 4 wherein the TCR is a MAGE A4 TCR and/or can bind MAGE-A4.

6. A modified T cell or population of modified T cells according to claim 5 wherein the TCR comprises an a chain amino acid sequence having at least 80% sequence identity to SEQ ID NO: 3.

7. A modified T cell or population of modified T cells according to claim 5 or claim 6 wherein the TCR comprises a b chain amino acid sequence having at least 80% sequence identity to SEQ ID NO: 5.

8. A nucleic acid or nucleic acid construct encoding the TCR and CD8 co-receptor according to any of the preceding claims.

9. A nucleic acid or nucleic acid construct according to claim 8 comprising;

i. a first nucleotide sequence encoding a CD8 co-receptor; and

ii. a second nucleotide sequence encoding a T cell receptor.

10. A nucleic acid or nucleic acid construct according to claim 8 or 9 wherein the CD8 co-receptor is CD8a.

11. A nucleic acid or nucleic acid construct according to claim 10 wherein the nucleotide sequence encoding CD8a comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 2.

12. A nucleic acid or nucleic acid construct according to any one of claims 8 to 10 wherein the TCR binds a cancer or tumour antigen or peptide thereof and/or is an affinity enhanced TCR.

13 A nucleic acid or nucleic acid construct according to any one of claims 7 to 1 1 wherein the TCR is a MAGEA4 TCR and/or can bind MAGE-A4.

14. A nucleic acid or nucleic acid construct according to claim 12 wherein the TCR comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 3.

15. A nucleic acid or nucleic acid construct according to claim 12 or claim 13 wherein the TCR comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 5.

16. A nucleic acid or nucleic acid construct according to any one of claims 12 to 14 wherein the nucleotide sequence encoding the TCR comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 4.

17. A nucleic acid or nucleic acid construct according to any one of claims 12 to 15 wherein the nucleotide sequence encoding the TCR comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 6.

18 A vector comprising a nucleic acid construct according to any one of claims 8 to 17.

19. A vector according to claim 18 wherein the vector is a lentiviral vector.

20. A viral particle comprising the nucleic acid or nucleic acid construct according to any one of claims 8 to 17 or a vector according to any one of claims 18 to 19.

21. A method of making the modified T cell or population of modified T cells according to any one of claims 1 to 7 comprising introducing one or more than one copy of the nucleic acid or nucleic acid construct of any one of claims 8 to 17 or a vector of either of claims 18 or 19 into a T cell or population of T cells, optionally wherein the nucleic acid or vector is comprised within a viral particle of claim 20,

21. A modified T cell or population of modified T cells comprising a nucleic acid or nucleic acid construct or vector according to any one of the claims 8 to 19 or produced according to the method of claim 21.

22. A pharmaceutical composition comprising the modified T cell or population of modified T cells according to any one of claims 1 to 7 or 21 , the nucleic acid or nucleic acid construct of any one of claims 8 to 17, the vector of either of claims 18 or 19 or viral particle of claim 20 and a pharmaceutically acceptable carrier.

23. The modified T cell or population of modified T cells according to any one of claims 1 to 7 or 21 , the nucleic acid or nucleic acid construct of any one of claims 8 to 17, the vector of either of claims 18 or 19 or viral particle of claim 20, or pharmaceutical composition of claim22 for use in therapy and/or medicine.

24. The modified T cell or population of modified T cells according to any one of claims 1 to 7 or 21 , the nucleic acid or nucleic acid construct of any one of claims 8 to 17, the vector of either of claims 18 or 19 or viral particle of claim 20, or pharmaceutical composition of claim22 for use in for use in the treatment of cancer and/or tumour optionally wherein the treatment is cancer immunotherapy therapy and/or adoptive T cell therapy, optionally autologous or allogenic adoptive T cell therapy.

25. A method of treating cancer and/or tumour in an individual comprising administering to the individual the modified T cell or population of modified T cells according to any one of claims 1 to 7 or 21 , the nucleic acid or nucleic acid construct of any one of claims 8 to 17, the vector of either of claims 18 or 19 or viral particle of claim 20, or pharmaceutical composition of claim22, optionally wherein the treatment is cancer

immunotherapy therapy and/or adoptive T cell therapy, optionally autologous or allogenic adoptive T cell therapy.

26. Use of the modified T cell or population of modified T cells according to any one of claims 1 to 7 or 21 , the nucleic acid or nucleic acid construct of any one of claims 8 to 17, the vector of either of claims 18 or 19 or viral particle of claim 20, or pharmaceutical composition of claim22 for use in for the manufacture of a medicament for the treatment of cancer and/or tumour, optionally wherein the treatment is cancer immunotherapy therapy and/or adoptive T cell therapy, optionally autologous or allogenic adoptive T cell therapy.

27. The modified T cell or population of modified T cells according to any one of claims 1 to 7 or 21 , the nucleic acid or nucleic acid construct of any one of claims 8 to 17, the vector of either of claims 18 or 19 or viral particle of claim 20, or pharmaceutical composition of claim22 for use according to claim 23 or 24, or in the method of claim 25 or for use of claim 26, wherein the cancer is a solid tumour.

28. The modified T cell or population of modified T cells according to any one of claims 1 to 7 or 21 , the nucleic acid or nucleic acid construct of any one of claims 8 to 17, the vector of either of claims 18 or 19 or viral particle of claim 20, or pharmaceutical composition of claim22 for use according to claim 23 or 24, or in the method of claim 25 or for use of claim 26 or claim 27, wherein the wherein the modified T cell or population of modified T cells, nucleic acid, vector, virus particle, or pharmaceutical is for use or used in combination with one or more further therapeutic agent optionally administered or for administration separately, sequentially or simultaneously

29. A method of engineering a modified T cell or population of modified T cells comprising:

i. providing a T cell or population of T cells;

ii. introducing the vector according to claim 18 or claim 19 into said T cell or population of T cells; and

iii. expressing said vector in the T cell or population of T cells.