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 CDR sequences which are N—C ordered:
CDR1 Heavy
Chain (HC)
SEQ ID NO: 309
SYGVH
CDR2 HC
SEQ ID NO: 310
VIWAGGTTNYNSALMS
CDR3 HC
SEQ ID NO: 311
DGHFHFDF
CDR1 Light
Chain (LC)
SEQ ID NO: 303
RASDIIYSNLA
CDR2 LC
SEQ ID NO: 304
AATNLAA
CDR3 LC
SEQ ID NO: 305
QHFWGSSIS
said affinity binding entity capable of binding HLA-A2/Tyr D369-377 in an MHC restricted manner.
2. An affinity binding entity comprising an antigen binding domain comprising CDR sequences which are N—C ordered:
CDR1 Heavy
Chain (HC)
SEQ ID NO: 293
TSGMGVS
CDR2 HC
SEQ ID NO: 294
HIYWDDDKRYNPSLKS
CDR3 HC
SEQ ID NO: 295
KDYGSSFYAMHY
CDR1 Light
Chain (LC)
SEQ ID NO: 287
KASQDIHNYIA
CDR2 LC
SEQ ID NO: 288
YTSTLQP
CDR3 LC
SEQ ID NO: 289
LQYDNLWT
said affinity binding entity capable of binding HLA-A2/TyrD 369-377 in an MHC restricted manner.
3. The affinity binding entity of claim 1 , being selected from the group consisting of an antibody, a chimeric antigen receptor (CAR) and a T-cell receptor (TCR).
4. The affinity binding entity of claim 1 , being an antibody.
5. The affinity binding entity of claim 1 , being a TCR.
6. The affinity binding entity of claim 1 , being a CAR.
7. The affinity binding entity of claim 1 , being a soluble entity.
8. The affinity binding entity of claim 3 , being a humanized antibody.
9. The affinity binding entity of claim 1 , comprising a therapeutic moiety.
10. The affinity binding entity of claim 4 , comprising a therapeutic moiety.
11. The affinity binding entity of claim 1 , comprising a detectable moiety.
12. The affinity binding entity of claim 3 , wherein said antibody is a single chain antibody, a bi-specific antibody or a full length antibody.
13. 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.
14. A cell comprising the expression vector of claim 13 .