I DOMAIN CHIMERIC ANTIGEN RECEPTOR SPECIFIC TO ICAM-1

• Main Author: JIN MOONSOO
• Format: Patent
• Language: Chinese; English
• Published: 23.10.2018
• Subjects: AGRICULTURE; ANIMAL HUSBANDRY; BEER; BIOCHEMISTRY; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES, AS HERBICIDES; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; DERIVATIVES THEREOF; ENZYMOLOGY; FISHING; FORESTRY; HUMAN NECESSITIES; HUNTING; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; PEPTIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTSTHEREOF; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPIRITS; SUGARS; TRAPPING; VINEGAR; WINE

The present invention relates to chimeric antigen receptors (CARs) specific to ICAM-1 comprising I domain of the alphaL subunit of human lymphocyte function-associated antigen 1 (LFA-1). The inventionparticularly relates to CARs comprising human I domains having different affinities (1 mM to 1 nM Kd) to ICAM-1. CAR T cells comprising human I domain having a low affinity (1 to 200 [mu]M Kd) to ICAM-1 can avoid targeting healthy tissues with basal ICAM-1 expression while simultaneously exhibiting increased potency and long-term efficacy against tumor tissues with high ICAM-1 expression. The present invention also relates to an adoptive cell therapy method for treating cancer by administering the CAR-T cells comprising human I domain to a subject suffering from cancer, whereby the CAR T cells bind to the cancer cells overexpressing ICAM-1 and kill the cancer cells. 本发明涉及对细胞间粘附分子-1(ICAM-1)特异性的嵌合抗原受体(CAR)，其包含人淋巴细胞功能相关抗原1(LFA-1)的α亚基的I结构域。本发明特别涉及包含人I结构域的CAR，所述人I结构域对ICAM-1具有不同的亲和力(1mM至1nM Kd)。包含对ICAM-1具有低亲和力(1-200μM