Sur-binding proteins against ERBB3
Embodiments concern constructs comprising surrogate light chain sequences. In particular, embodiments concern constructs that can bind to ErbB3 and aspects relating to such constructs.
1. A sur-binding protein comprising:
(i) a surrogate light chain (SLC) sequence comprising, from N-terminus to C-terminus, a VpreB1 sequence covalently fused to a λ5 sequence, wherein the SLC sequence comprises the amino acid sequence of SEQ ID NO: 276; and
(ii) a heavy chain variable region amino acid sequence comprising:
(a) a heavy chain complementarity determining region (CDR) 1 sequence comprising SEQ ID NO: 39, a heavy chain CDR2 sequence comprising SEQ ID NO: 40, and a heavy chain CDR3 sequence comprising SEQ ID NO: 41; or
(b) a heavy chain CDR1 sequence comprising SEQ ID NO: 43, a heavy chain CDR2 sequence comprising SEQ ID NO: 44, and a heavy chain CDR3 sequence comprising SEQ ID NO: 45;
wherein the heavy chain variable region amino acid sequence is conjugated to the SLC sequence to form a sur-binding protein, and wherein said sur-binding protein specifically binds to an ErbB3 protein.
2. The sur-binding protein of claim 1 , wherein the ErbB3 protein comprises the sequence of SEQ ID NO: 36.
3. The sur-binding protein of claim 1 , wherein the SLC sequence is covalently conjugated to the heavy chain variable region amino acid sequence.
4. The sur-binding protein of claim 1 , wherein the SLC sequence is non-covalently conjugated to the heavy chain variable region amino acid sequence to form a dimeric complex.
5. A bispecific sur-binding protein comprising:
(i) a first surrogate light chain (SLC) sequence comprising, from N-terminus to C-terminus, a VpreB1 sequence covalently fused to a λ5 sequence, wherein the first SLC sequence comprises the amino acid sequence of SEQ ID NO: 276;
(ii) a first heavy chain variable region amino acid sequence comprising:
(a) a heavy chain complementarity determining region (CDR) 1 sequence comprising SEQ ID NO: 39, a heavy chain CDR2 sequence comprising SEQ ID NO: 40, and a heavy chain CDR3 sequence comprising SEQ ID NO: 41; or
(b) a heavy chain CDR1 sequence comprising SEQ ID NO: 43, a heavy chain CDR2 sequence comprising SEQ ID NO: 44, and a heavy chain CDR3 sequence comprising SEQ ID NO: 45,
wherein the first heavy chain variable region amino acid sequence is paired with the first SLC sequence to form a first sur-binding protein binding site, wherein the first sur-binding protein binding site binds to an ErbB3 protein; and
(iii) a second SLC sequence comprising, from N-terminus to C-terminus, a VpreB1 sequence covalently fused to a λ5 sequence, wherein the second SLC sequence comprises the amino acid sequence of SEQ ID NO: 276; and
(iv) a second heavy chain variable region amino acid sequence that is paired with the second SLC sequence to form a second sur-binding protein site, wherein the second sur-binding protein site binds to a second target.
6. A method for suppressing tumor growth in a subject comprising providing an ErbB3 sur-binding protein to a tumor in the subject, wherein the tumor comprises a cell that expresses ErbB3, thereby suppressing tumor growth, wherein the ErbB3 sur-binding protein comprises:
(i) a surrogate light chain (SLC) sequence comprising, from N-terminus to C-terminus, a VpreB1 sequence covalently fused to a λ5 sequence, wherein the SLC sequence comprises the amino acid sequence of SEQ ID NO: 276; and
(ii) a heavy chain variable region amino acid sequence comprising:
(a) a heavy chain complementarity determining region (CDR) 1 sequence comprising SEQ ID NO: 39, a heavy chain CDR2 sequence comprising SEQ ID NO: 40, and a heavy chain CDR3 sequence comprising SEQ ID NO: 41; or
(b) a heavy chain CDR1 sequence comprising SEQ ID NO: 43, a heavy chain CDR2 sequence comprising SEQ ID NO: 44, and a heavy chain CDR3 sequence comprising SEQ ID NO: 45;
wherein the heavy chain variable region amino acid sequence is conjugated to the SLC sequence to form the ErbB3 sur-binding protein.
7. The method of claim 6 , wherein the tumor cell is selected from the group consisting of squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, gastric cancer, pancreatic cancer, glial cell tumors, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, melanoma, colorectal cancer, endometrial carcinoma, salivary gland carcinoma, renal cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma and of head and neck cancer.