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[BioS 레터]Flagging the tumor.."OV+CAR-T 가능성" - 바이오스펙테이터

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[BioS 레터]Flagging the tumor.."OV+CAR-T 가능성"

입력 2020-09-29 15:43 수정 2020-10-06 11:34

최용빈 객원연구원

이 기사는 '프리미엄 뉴스서비스 BioS+' 기사입니다.
항암 바이러스(Oncolytic virus)와 CAR(Chimeric antigen receptor)-T 세포의 병용요법의 가능성 제시한 논문, Science Translational Medicine에 게재

최근 수년간 면역관문억제제(Immune checkpoint inhibitor) 등의 항체 약물 및 CAR(Chimeric antigen receptor)-T 세포를 활용한 세포 치료제 등의 항암면역 치료제들의 미국 FDA 승인이 본격화됨에 따라, 항암면역치료는 가히 기존 항암치료의 패러다임을 혁신적으로 바꾸어 놓았다고 평가된다. 그럼에도 불구하고, 항암면역치료는 표적으로 하는 항원 단백질의 발현이 고형암(Solid tumor)의 암세포 외에 정상 세포에서도 발현될 수 있다는 점과 개별 환자들 사이의, 또는 단일 환자의 종양 내에서 해당 항원의 발현이 불규칙적이고(Non-uniformity), 이질적(Heterogeneity)이라는 점 등에 의해 임상적 한계를 가지고 있다.

항암면역 치료의 궁극적인 목표는 특정 환자군 또는 특정 암종에 국한되지 않고 다양한 암 환자 및 다수의 암종에 보편적으로 사용될 수 있는 치료법(Universal therapy)을 개발하는 것에 있다고 볼 수 있다. 하지만 최근 단일세포 기반 분석기법(Single cell RNA-sequencing, Mass-cytometry 등)을 통해 단일 종양내에서도 매우 다양한 특성을 갖는 암세포가 존재하며, 시간에 따라 그 특성과 분포가 변화한다는 사실이 보고되었다는 점을 고려하면, 보편적으로 적용 가능한 항암면역 치료법(Universal cancer immunotherapy)의 개념은 지나치게 이상적이라는 생각이 들기도 한다. 그런데 이상적으로 보이는 ‘보편적 항암 면역치료’의 가능성을 항암 바이러스(Oncolytic virus)와 CAR(Chimeric antigen receptor)-T 세포의 병용요법을 통해 제시한 논문이 지난 9월 2일 'Science Translational Medicine'에 게재되었다.

항암 바이러스(Oncolytic virus)란?

용해성 바이러스(Lytic virus)는 숙주 세포를 감염시켜 자기 물질을 복제하고, 숙주세포를 터뜨림으로써 다른 숙주세포로 감염을 이어나간다. 숙주 세포를 죽이는 용균성 바이러스의 특성을 암세포를 대상으로 활용할 수 있을까? 연구자들은 이러한 질문에서 항암 바이러스의 아이디어를 얻었고, 암세포에서 특징적으로 나타나는 비정상적 세포 내 신호전달 경로 활성화 및 단백질 발현 양상을 활용하면 암세포를 선택적으로 감염하고, 암세포에서만 자기 물질을 복제하여 결국 암세포를 선택적으로 사멸시키는 항암 바이러스를 설계할 수 있음을 알게 되었다.

항암 바이러스를 이용한 항암치료는 2000년대에 들어 본격화 되었는데, 2005년 중국 CFDA는 상하이 선웨이 바이오텍(Shanghai Sunway Biotech)의 아데노바이러스(Adenovirus) 기반 항암 바이러스인 Oncorine과 화학요법(Chemotherapy)과의 병용요법을 비인두암(Nasopharyngeal carcinoma) 치료제로 승인함으로써 항암 바이러스 의약품 시대의 시작을 알렸다....

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