Ror1-specific chimeric antigen receptors (car) with humanized targeting domains
AssigneeJulius-Maximilians-UniversitäT WüRzburg
InventorsMichael HUDECEK, Andreas MADES
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Abstract
The invention relates to chimeric antigen receptors (CAR) with a humanized targeting domain specific to the antigen ROR1. The invention encompasses the polynucleotides, vectors encoding said CARs and the isolated cells expressing them at their surface, in particularly for their use in immunotherapy.
Claims24
A ROR1-specific CAR comprising:
- a humanized targeting domain obtainable by humanization of a ROR1-binding fragment of a monoclonal antibody capable of binding to ROR1, wherein said monoclonal antibody is selected from the group consisting of the monoclonal antibodies R11, R12 and 2A2.
A ROR1-specific CAR comprising a humanized targeting domain capable of binding to ROR1, wherein the humanized targeting domain comprises, preferably in an N- to C-terminal order:
- a) an antibody heavy chain variable domain amino acid sequence selected from the group consisting of:
- a1) the amino acid sequence of SEQ ID No:
- 1 or an amino acid sequence at least 90% identical thereto;
- a2) the amino acid sequence of SEQ ID No:
- 3 or an amino acid sequence at least 90% identical thereto;
- or
- a3) the amino acid sequence of SEQ ID No:
- 5 or an amino acid sequence at least 90% identical thereto;
- and
- b) an antibody light chain variable domain amino acid sequence selected from the group consisting of:
- b1) the amino acid sequence of SEQ ID No:
- 2 or an amino acid sequence at least 90% identical thereto;
- b2) the amino acid sequence of SEQ ID No:
- 4 or an amino acid sequence at least 90% identical thereto;
- or
- b3) the amino acid sequence of SEQ ID No:
- 6 or an amino acid sequence at least 90% identical thereto.
6-12. (canceled)
A combination of CARs comprising at least a first and a second CAR, the combination being ROR1-specific, wherein said first and said second CAR are present on different polypeptide chains, and wherein:
- c) said first CAR comprises a first humanized targeting domain comprising an antibody heavy chain variable domain amino acid sequence selected from the group consisting of:
- c1) the amino acid sequence of SEQ ID No:
- 1 or an amino acid sequence at least 90% identical thereto;
- c2) the amino acid sequence of SEQ ID No:
- 3 or an amino acid sequence at least 90% identical thereto;
- or
- c3) the amino acid sequence of SEQ ID No:
- 5 or an amino acid sequence at least 90% identical thereto;
- and
- d) said second CAR comprises a second humanized targeting domain comprising an antibody light chain variable domain amino acid sequence selected from the group consisting of:
- d1) the amino acid sequence of SEQ ID No:
- 2 or an amino acid sequence at least 90% identical thereto;
- d2) the amino acid sequence of SEQ ID No:
- 4 or an amino acid sequence at least 90% identical thereto;
- or
- d3) the amino acid sequence of SEQ ID No:
- 6 or an amino acid sequence at least 90% identical thereto.
18-32. (canceled)
36-45. (canceled)
53-57. (canceled)
Dependencies are inferred from the claim text.