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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 City of hope, 뇌종양 치료 CAR-T 임상1상 자금 지원받아 - 바이오스펙테이터

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City of hope, 뇌종양 치료 CAR-T 임상1상 자금 지원받아

입력 2017-10-12 11:21 수정 2017-10-12 11:31

바이오스펙테이터 이은아 기자

CIRM 재단서 임상1상 지원금 1280만弗 확보.."뇌실 내 투여(ICV)와 두개 내(Intracavitary) 투여"로 임상예정

뇌종양 치료를 위한 CAR-T 치료제의 효과적인 전달 방법은 무엇일까?

City of hope는 악성뇌종양 환자를 치료하기 위한 IL13Rα2 타깃 CAR-T치료제(MB-101) 임상1상 시험을 위해 캘리포니아 재생의학연구지원재단(CIRM, California Institute for Regenerative Medicine)으로부터 1280만 달러를 지원받았다고 11일 발표했다.

이 자금으로 환자의 뇌척수액과 종양 부위에 CAR-T치료제를 주입하는 2가지 접근법으로 전달 효과를 확인할 예정이다. 진행할 임상연구 중 하나는 뇌실 내 투여(intracerebroventricular, ICV)로 뇌척수액에 확산된 MB-101 CAR-T 치료제의 효능을 평가할 예정이고, 또 다른 연구는 뇌종양 조직에 직접 주입하는 두개 내(intracavitary) 투여와 ICV 투여로 확인하게 된다.

최근 뇌종양 치료를 위한 CAR-T 치료제의 초기 임상연구가 시작됐지만 뇌 종양에 효과적으로 전달하는 방법에 대해 논의가 계속되고 있다. 이번 임상시험 결과가 기대되는 이유다.

특히 MB-101은 지난해 12월 치료가 어려운 뇌종양에서 처음으로 CAR-T 치료제의 효능을 확인해 더욱 주목받고 있다. NEJM 저널에 발표한 내용에 따르면 CAR-T 치료제를 220일간 두개 내 투여시 두개 내와 척추에 생긴 종양에서 모두 종양소실이 관찰됐고, 뇌척수액에서 사이토카인과 면역세포가 증가되는 것을 확인했다. T세포의 활성과 종양소실 사이의 연관성에 대해 보여준 것이다. 이러한 효과는 CAR-T 치료제 투여한지 7.5개월 후에도 지속됐다.

당시 임상시험에서 CAR-T 치료제는 종양조직 내 직접 주입한 후 뇌실 내(intraventricular) 주입으로 전환한 방법을 따랐다. 이번 지원금으로 진행될 두 임상시험 방법도 이 연구에서 착안한 것이다.

마누엘 리치먼(Manuel Litchman) 머스탱바이오(Mustang Bio) 대표는 “지난해 말 교모세포종 환자에게 MB-101를 심실 시스템에 주입했을 때 전례 없는 완전관해 반응을 보이며 강력한 치료 가능성을 보여줬다. 이번 자금으로 MB-101의 가장 효과적인 전달 방법을 연구하기 위한 임상1상을 확장해 연구할 수 있게 됐다”고 말했다.

한편 미국 생명공학회사인 머스탱바이오(Mustang Bio)에서 개발한 MB-101은 교모세포종(GBM) 세포표면에 50% 이상 발현한다고 알려진 IL13Rα2을 표적한 CAR-T 치료제다. MB-101은 부작용은 감소시키고 항암효과와 지속성은 향상시키기 위한 방법으로 설계됐다. 정상 조직을 타깃하는 부작용을 줄이기 위해서 IL13Rα1와의 결합은 감소시키고 IL13Rα2와의 결합은 높이도록 IL-13 수용체 리간드인 IL-13이 세포표면에 발현되도록 했다. Fc 수용체와의 오프타깃(off target) 상호작용을 줄이기 위해 IgG4-Fc 링커에 돌연변이도 포함시켰다. 또한 신호자극 보조인자인 41BB(CD137)를 추가해 항암효과를 높이고, 중추 기억T세포(central memory T)에서 CAR를 발현시킴으로써 CAR-T 치료제 효과가 오래 지속되도록 했다.

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