FIELD: medicine.
SUBSTANCE: group of inventions relates to immunology and therapy of diseases or conditions associated with high expression of human ROR1. Proposed are antibodies specifically recognising human ROR1, antibody-drug conjugates (ADCs), chimeric antigenic receptors (CARs), compositions based thereon, and applications thereof. The antibody or the antigen-binding fragment of the antibody includes heavy and light chain CDRs sequences displayed in (1) SEQ ID NO:27 to 29 and SEQ ID NO:66 to 68; (2) SEQ ID NO:30 to 32 and SEQ ID NO:69 to 71; (3) SEQ ID NO:33 to 35 and SEQ ID NO:72 to 74; (4) SEQ ID NO:36 to 38 and SEQ ID NO:75 to 77; (5) SEQ ID NO:39 to 41 and SEQ ID NO:78 to 80; (6) SEQ ID NO:42 to 44 and SEQ ID NO:81 to 83; (7) SEQ ID NO:45 to 47 and SEQ ID NO:84 to 86; (8) SEQ ID NO:48 to 50 and SEQ ID NO:87 to 89; (9) SEQ ID NO:51 to 53 and SEQ ID NO:90 to 92; (10) SEQ ID NO:54 to 56 and SEQ ID NO:93 to 95; (11) SEQ ID NO: 57 to 59 and SEQ ID NO:96 to 98; (12) SEQ ID NO:60 to 62 and SEQ ID NO:99 to 101; or (13) SEQ ID NO:63 to 65 and SEQ ID NO:102 to 104. The proposed anti-ROR1 antibodies have high affinity. The CARs and CAR-T cells constructed using the above anti-hROR1 binding domains exhibit high effectiveness in vitro. The ADCs including the hROR1-specific antibody execute effective killing of hROR1-specific cells.
EFFECT: inventions allow for effective therapy of human cancer associated with the expression of ROR1.
37 cl, 29 dwg, 16 tbl, 23 ex
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Authors
Dates
2022-02-09—Published
2017-01-20—Filed