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348 Warning: mysql_real_escape_string(): Access denied for user 'et1ssh96'@'localhost' (using password: NO) in /service/web/biospcmbl/comlib/dblib.php on line 30 Warning: mysql_real_escape_string(): A link to the server could not be established in /service/web/biospcmbl/comlib/dblib.php on line 30 Warning: mysql_query(): Access denied for user 'et1ssh96'@'localhost' (using password: NO) in /service/web/biospcmbl/comlib/dblib.php on line 530 Warning: mysql_query(): A link to the server could not be established in /service/web/biospcmbl/comlib/dblib.php on line 530 Warning: mysql_fetch_array() expects parameter 1 to be resource, boolean given in /service/web/biospcmbl/comlib/dblib.php on line 531 이수앱지스 'ErbB3 항체', 세툭시맙 내성극복 가능성 확인 - 바이오스펙테이터

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이수앱지스 'ErbB3 항체', 세툭시맙 내성극복 가능성 확인

입력 2018-04-24 14:39 수정 2018-04-26 23:51

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2018 AACR서 발표..‘ISU104‘ 동물모델서 항암효과 70% 이상, 세툭시맙 내성 가능성도 확인, 병용시 항암효과↑

▲2018 미국 암학회(AACR)에서 이수앱지스 포스터 발표 모습 (사진: 회사 제공)

이수앱지스가 ErbB3 항체 ‘ISU104’의 비임상 데이터를 2018 미국암학회(AACR)에서 처음으로 선보였다. 다양한 암종을 보유한 이종이식 동물모델에서 70% 이상의 종양성장 억제효과를 비롯해 기존 표적치료제인 ‘얼비툭스(성분명 세툭시맙)’와 병용투여 및 내성 극복 가능성을 제시했다.

현재 ISU104은 국내 임상1상 단계로 진행성 고형암 환자에서 안전성, 내약성 및 약동학적 특성을 평가하고 있다. 임상시험은 용량증량 코호트(dose-escalation cohort)와 용량확대 코호트(dose-expansion cohort)로 구분해 수행 중이다.

ISU104는 ErbB3를 타깃하는 완전인간 단일클론항체로 파지 디스플레이 라이브러리로부터 분리됐다. 상피세포성장인자 수용체 계열(EGFR family, ErbB1, ErbB2, ErbB3, ErbB4)에 속하는 ErbB3는 암의 발생과 진행에 관여한다. 활성화된 ErbB 수용체가 인산화된 세포질 도메인을 통해 다양한 신호분자와 결합해 종양 발생(oncogenic) 신호전달 경로를 활성화시키는 것이다.

특히 ErbB3는 대장암, 두경부암에서 표적치료제, 화학항암제에 대한 약물내성의 주요 원인 중 하나로 알려져 있다. 이는 ErbB3의 우회적인 활성화와 그에 따른 PI3K/AKT 신호전달이 지속적으로 활성화되는 것에서 비롯된다. 이에 대해 ISU104는 기존 항암제와 병용투여 효과와 내성 극복 효능을 가진다는 차별성이 갖는다. 2018 AACR 학회에서 발표한 포스터 내용을 통해, 비임상시험에서 입증한 ISU104의 항암 작용기전과 그에 따른 효과, 세툭시맙 내성극복 가능성에 대해 자세히 살펴봤다.

◇ ‘ISU104‘ 동물모델서 항암효과 70% 이상..세툭시맙 병용시 효능 증진

먼저, ISU104은 ErbB3가 발현하는 암 세포주에서 ErbB3에 특이적으로 결합하는 것을 확인했다. 또 ISU104의 용량에 비례해(3nM, 30nM, 300nM) 리간드인 HRG(heregulin)와 ErbB3의 결합을 억제했다. 유방암 세포주에서 ISU104를 처리하자 ErbB3와 ErbB2의 이량체(dimer) 형성을 억제하고, ErbB3 단백질 발현을 감소시켰다. I...

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