RECOMBINANT PROTEIN THAT RECOGNIZES CADM1, AND PHARMACEUTICAL COMPOSITION FOR TREATMENT OF CANCERS COMPRISING SAME AS ACTIVE INGREDIENT

• Main Authors: KANG, Seok Jin, PARK, Si Won, CHIN, Hwa Sup, YANG, Jun, PARK, In Byung, LEE, Hyeon Jeong, LEE, Chang Hee, CHUN, Tae Hoon, LEE, Na Young
• Format: Patent
• Language: English; French; Korean
• Published: 04.05.2023
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

The present invention relates to a recombinant protein that is toxic to CADM1-expressing cells and, more particularly, to a recombinant protein comprising a CRTAM protein having a high affinity for CADM1 and a pharmaceutical composition for preventing or treating CADM1-expressing cancers using same. An extracellular domain of CRTAM from among the recombinant proteins of the present invention recognizes CADM1 and binds to specific CADM1-expressing cancer cells, and the human immunoglobulin G1 heavy chain constant region (human IgG1 heavy chain constant region) binds to IgG receptors (FcγRIIIa, CD16a) of a natural killer cell and transmits an activation signal to the inside of the natural killer cell, such that the recombinant protein can have cytotoxicity against CADM1-expressing cells and can be used by binding a drug conjugate thereto. Therefore, the recombinant protein according to the present invention can be effectively used as a therapeutic agent having cytotoxicity specifically to CADM1-expressing cells. La présente invention concerne une protéine recombinante qui est toxique pour les cellules exprimant CADM1 et, plus particulièrement, une protéine recombinante comprenant une protéine CRTAM ayant une affinité élevée pour CADM1 et une composition pharmaceutique pour la prévention ou le traitement de cancers exprimant CADM1 l'utilisant. Un domaine extracellulaire de CRTAM parmi les protéines recombinantes selon la présente invention reconnaît CADM1 et se lie à des cellules cancéreuses exprimant CADM1 spécifiques, et la région constante de chaîne lourde d'immunoglobuline G1 humaine (région constante de chaîne lourde d'IgG1 humaine) se lie aux récepteurs d'IgG (FcγRIIIa, CD16a) d'une cellule tueuse naturelle et transmet un signal d'activation à l'intérieur de la cellule tueuse naturelle, de telle sorte que la protéine recombinante peut avoir une cytotoxicité contre les cellules exprimant CADM1 et peut être utilisée par liaison d'un conjugué de médicament à celle-ci. Par conséquent, la protéine recombinante selon la présente invention peut être utilisée de manière efficace en tant qu'agent thérapeutique ayant une cytotoxicité spécifique à des cellules exprimant CADM1. 본 발명은 CADM1을 발현하는 세포에 독성을 갖는 재조합 단백질에 관한 것으로, 구체적으로 CADM1에 높은 친화력을 가진 CRTAM 단백질을 포함하는 재조합 단백질 및 이를 이용하여 CADM1을 발현하는 암에 대한 예방 또는 치료용 약학 조성물에 관한 것이다. 본 발명의 재조합 단백질 중 CRTAM의 세포외 도메인은 CADM1을 인지하여 CADM1이 발현되는 특정 암세포와 결합하고, 재조합 단백질의 인간 이뮤노글로불린 G1 중쇄 불변 영역부위(human IgG1 heavy chain constant region)는 자연살생세포의 IgG 수용체(FcγRIIIa, CD16a)와 결합하여 자연살생세포 내부로 활성화 신호를 전달해 줌으로써 CADM1이 발현되는 세포에 대한 세포독성을 가질 수 있게 할 뿐만 아니라 상기 재조합 단백질에 약물 접합체를 결합시켜 이용할 수도 있다. 따라서, 본 발명에 의한 재조합 단백질은 CADM1이 발현되는 세포에 특이적으로 세포독성을 갖는 치료제로서 유용하게 사용될 수 있다.