Affinity entities comprising a TCR-like antibody binding domain with high affinity and fine specificity and uses of same
Affinity binding entities having TCRL binding domain and methods of their use are provided. More specifically these compositions bind HLA-A2/WT1+, HLA-A2/MAGE-A4, HLA-A2/MAGE-A9, HLA-A2/PAP or HLA-A2/TyrD+ cells and as such can be used in diagnostics and therapy.
1. An affinity binding entity comprising an antigen binding domain comprising:
(i) CDR sequences of an immunoglobulin heavy chain which are N—C ordered:
CDR1 HC
SEQ ID NO: 341
GYWIE
CDR2 HC
SEQ ID NO: 342
EILPGSGGTNYNEKFKG
CDR3 HC
SEQ ID NO: 343
DSNSFTY;
and
(ii) CDR sequences of an immunoglobulin light chain which are N—C ordered:
CDR1 LC
SEQ ID NO: 335
SVSSSVDYIH
CDR2 LC
SEQ ID NO: 336
STSILAS
CDR3 LC
SEQ ID NO: 337
QQRSSYPPT,
wherein said affinity binding entity is capable of binding HLA-A2/MAGE-A4 230-239 in an MHC restricted manner.
2. The affinity binding entity of claim 1 , being selected from the group consisting of an antibody, a T-cell receptor (TCR), and a chimeric antigen receptor (CAR).
3. The affinity binding entity of claim 1 , being an antibody.
4. The affinity binding entity of claim 1 , being a TCR.
5. The affinity binding entity of claim 1 , being a CAR.
6. The affinity binding entity of claim 1 , being a soluble entity.
7. The affinity binding entity of claim 2 , being a humanized antibody.
8. The affinity binding entity of claim 1 , further comprising a therapeutic moiety.
9. The affinity binding entity of claim 2 , further comprising a therapeutic moiety.
10. The affinity binding entity of claim 1 , further comprising a detectable moiety.
11. The affinity binding entity of claim 2 , wherein said antibody is a single chain Fv (scFv), a bi-specific antibody, or a full-length antibody.
12. An expression vector comprising a polynucleotide comprising a nucleic acid sequence encoding the affinity binding entity of claim 1 operably linked to a cis-acting regulatory element.
13. A cell comprising the expression vector of claim 12 .
14. An in vitro method of detecting a cancer cell, comprising:
contacting the cell with the antibody of claim 2 , under conditions which allow immunocomplex formation, and
detecting the presence or level thereof of said immunocomplex,
wherein a presence of said immunocomplex, or level thereof, is indicative of the cancer cell,
wherein the cancer is selected from the group consisting of melanoma, ovarian cancer, T cell leukemia/lymphoma, testicular cancer, head and neck cancer, bladder cancer, and esophagus cancer.
15. A method of diagnosing cancer in a subject in need thereof, comprising:
contacting a cell of the subject with the antibody of claim 2 , under ex vivo conditions which allow immunocomplex formation, and
detecting the presence or level thereof of said immunocomplex,
wherein a presence of said immunocomplex or level thereof is indicative of the cancer,
wherein the cancer is selected from the group consisting of melanoma, ovarian cancer, T cell leukemia/lymphoma, testicular cancer, head and neck cancer, bladder cancer, and esophagus cancer.
16. A pharmaceutical composition comprising the affinity binding entity of claim 2 , the expression vector of claim 12 or the cell of claim 13 and a carrier or excipient.