Chimeric antigen receptor to carbohydrate antigens
OwnerVered PADLER-KARAVANI, Yafit ATIYA-NASAGI +6inventors
InventorsVered PADLER-KARAVANI, Yafit ATIYA-NASAGI, Ron AMON, Anat GLOBERSON LEVIN, Tova WAKS, Moran RAWET-SLOBODKIN, Lihi NINIO MANY, Zelig ESHHAR
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Abstract
The present invention discloses chimeric antigen receptors that specifically recognize and bind to SLe A carbohydrate antigen with high specificity and selectivity. The invention further provides lymphocytic cells, such as T cells, comprising said CARs, compositions comprising said cells or CARs as well as uses thereof.
Claims21
1-53. (canceled)
A chimeric antigen receptor (CAR) comprising an antigen binding domain that binds specifically to Sialyl Lewis A glycan (SLeA), wherein the antigen binding domain comprises three complementarity determining regions (CDRs) and four framework (FR) domains of a heavy-chain variable domain (VH) having amino acid sequence as set forth in SEQ ID NO:
- 1 and three CDRs and four FRs of a light-chain variable domain (VL) having amino acid sequence as set forth in SEQ ID NO:
- 4, or an analog thereof having at least 90% sequence identity to said sequences.
The CAR according to claim 53, wherein the VH-CDR1 comprises amino acid sequence selected from SEQ ID NOs:
- 6 and 30, the VH-CDR2 comprises amino acid sequence selected from 7 and 31, the VH-CDR3 comprises amino acid sequence SEQ ID NO:
- 8, and CDRs 1, 2, and 3 of the VL domain comprise amino acid sequences SEQ ID NOs:
- 9, 10, and 11, respectively.
The CAR according to claim 53, wherein:
- (i) the VH-CDR 1, 2 and 3 comprise amino acid sequences SEQ ID NOs:
- 30, 12, and 8, respectively, the VL-CDRs 1, 2 and 3 comprise amino acid sequences SEQ ID NOs:
- 9, 10 and 11, respectively, VH-FRs 1, 2 and 4 comprise amino acid sequences SEQ ID NOs:
- 39, 42 and 43, respectively, and the VL-FR 1 comprises acid sequences SEQ ID NO:
- 44;
- (ii) the CDRs 1, 2, and 3 of the VH domain comprises amino acid sequences SEQ ID NOs:
- 30, 36 and 8, respectively, the CDRs 1, 2, and 3 of the VL domain comprise amino acid sequences SEQ ID NOs:
- 9, 10 and 11, the VH-FRs 1, 2 and 4 comprise amino acid sequences SEQ ID NOs:
- 40, 42 and 43, respectively, and the VL-FR1 comprises amino acid sequences SEQ ID NO:
- 44;
- (iii) the CDRs 1, 2, and 3 of the VH domain comprise amino acid sequences SEQ ID NOs:
- 30, 36 and 8, respectively, the CDRs 1, 2, and 3 of the VL domain comprise amino acid sequences SEQ ID NOs:
- 9, 10 and 11, respectively, the VH-FRs 1, 2, 3 and 4 comprise amino acid sequences SEQ ID NOs:
- 40, 42, 45 and 43, respectively, and the VL-FR1, 2, 3 and 4 comprise amino acid sequences SEQ ID NOs:
- 44, 46, 47 and 48, respectively;
- or
- (iv) the VH domain comprises amino acid sequence SEQ ID NO:
- 3 and the VL domain comprises amino acid sequence SEQ ID NO:
- 5.
The CAR according to claim 53, characterized by at least one of:
- (i) the CAR further comprising at least one conservative substitution in the framework(s) of the VH domain and/or VL domain, wherein the resulted VH domain has at least 90% sequence identity to SEQ ID NO:
- 3 and/or the resulted VL domain has at least 90% sequence identity to SEQ ID NO:
- 5;
- (ii) the VH and the VL domains are linked by a spacer to form a single chain variable fragment (scFv);
- and
- (iii) wherein the VH and the VL domains are linked by a spacer to form a scFv, wherein the spacer comprises amino acid sequence comprising from 2 to 6 repetitions of the amino acid sequence set forth in SEQ ID NO:
- 16.
The CAR according to claim 53, wherein the CAR comprises a transmembrane domain (TM domain), a costimulatory domain and an activation domain.
The CAR according to claim 53, comprising amino acid sequence selected from SEQ ID NO:
- 20 and 38.
A nucleic acid molecule, encoding the CAR according to claim 53 or the construct or vector comprising the nucleic acid molecule.
Dependencies are inferred from the claim text.