High avidity HPV T-cell receptors
The present invention pertains to novel high avidity antigen recognizing constructs against Human Papilloma Virus antigens. The invention provides novel T cell receptor (TCR) based molecules which are selective and specific for HPV 16/18 proteins E5, E6 and E7. The TCR of the invention, and HPV antigen-binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of HPV infection, as well as for the diagnosis, treatment and prevention of HPV infection mediated secondary diseases as HPV infection caused cancers, such as cervical, nasopharyngeal or head and neck cancer. Further provided are nucleic acids encoding the proteins of the invention, and recombinant cells expressing the same.
1. An antigen recognizing construct comprising a T cell receptor (TCR), or an antigen binding fragment thereof, wherein the TCR or the antigen binding fragment thereof is composed of a TCR α chain sequence and a TCR β chain sequence, wherein
(i) the TCR α chain sequence comprises an α chain complementary determining region 3 (CDR3), wherein an amino acid sequence of the α chain CDR3 comprises only one sequence selected from the group consisting of SEQ ID Nos: 9, 10, 12, 14, 16, 18, 21, 23, 25, and 27, and
(ii) the TCR β chain sequence comprises a β chain CDR3; wherein an amino acid sequence of the β chain CDR3 comprises only one sequence selected from the group consisting of SEQ ID Nos: 11, 13, 15, 17, 19, 20, 22, 24, 26, and 28.
2. The antigen recognizing construct according to claim 1 , wherein said TCR comprises a CDR1 and a CDR2 having sequences as set forth in SEQ ID NOs: 29 and 31; or 30 and 31; or 32 and 33; or 34 and 35; or 36 and 37; or 38 and 39; or 38 and 40; or 41 and 42; or 43 and 44; or 45 and 46; or 47 and 48.
3. The antigen recognizing construct according to claim 1 , wherein said TCR comprises variable sequences as set forth in SEQ ID NOs: 29 and 31; or 30 and 31; or 32 and 33; or 34 and 35; or 36 and 37; or 38 and 39; or 38 and 40; or 41 and 42; or 43 and 44; or 45 and 46; or 47 and 48.
4. A nucleic acid encoding for an antigen recognizing construct according to claim 1 .
5. A vector comprising a nucleic acid according to claim 4 .
6. An isolated host cell comprising an antigen recognizing construct according to claim 1 .
7. The host cell according to claim 6 , comprising a lymphocyte.
8. An isolated host cell comprising a nucleic acid according to claim 4 .
9. An isolated host cell comprising a vector according to claim 5 .
10. The antigen recognizing construct according to claim 1 , wherein the amino acid sequence of the α chain CDR3 consists of SEQ ID No. 9 or 10, and wherein the amino acid sequence of the β chain CDR consists of SEQ ID No. 11.
11. The antigen recognizing construct according to claim 1 , wherein the amino acid sequence of the α chain CDR3 consists of SEQ ID No. 12, and wherein the amino acid sequence of the β chain CDR consists of SEQ ID No. 13.
12. The antigen recognizing construct according to claim 1 , wherein the amino acid sequence of the α chain CDR3 consists of SEQ ID No. 14, and wherein the amino acid sequence of the β chain CDR consists of SEQ ID No. 15.
13. The antigen recognizing construct according to claim 1 , wherein the amino acid sequence of the α chain CDR3 consists of SEQ ID No. 16, and wherein the amino acid sequence of the β chain CDR consists of SEQ ID No. 17.
14. The antigen recognizing construct according to claim 1 , wherein the amino acid sequence of the α chain CDR3 consists of SEQ ID No. 18, and wherein the amino acid sequence of the β chain CDR consists of SEQ ID No. 20.
15. The antigen recognizing construct according to claim 1 , wherein the amino acid sequence of the α chain CDR3 consists of SEQ ID No. 21, and wherein the amino acid sequence of the β chain CDR consists of SEQ ID No. 22.
16. The antigen recognizing construct according to claim 1 , wherein the amino acid sequence of the α chain CDR3 consists of SEQ ID No. 23, and wherein the amino acid sequence of the β chain CDR consists of SEQ ID No. 24.
17. The antigen recognizing construct according to claim 1 , wherein the amino acid sequence of the α chain CDR3 consists of SEQ ID No. 25, and wherein the amino acid sequence of the β chain CDR consists of SEQ ID No. 26.
18. The antigen recognizing construct according to claim 1 , wherein the amino acid sequence of the α chain CDR3 consists of SEQ ID No. 27, and wherein the amino acid sequence of the β chain CDR consists of SEQ ID No. 28.
19. The antigen recognizing construct according to claim 1 , wherein the amino acid sequence of the α chain CDR3 consists of SEQ ID No, 19, and wherein the amino acid sequence of the β chain CDR consists of SEQ ID No. 20.