CAR-T 란?
CAR-T 는 chimeric antigen receptor T-cell(키메릭 항원 수용체 T세포)의 약자이다.
chimeric(키메릭)이라는 말의 어원은 그리스 신화에 등장하는 머리는 사자, 몸통은 염소, 꼬리는 뱀으로 이루어진 괴물 키마이라에서 유래한 단어로, 하나의 생물체 안에 유전 형질이 다른 세포가 함께 존재하는 것을 말한다.
CAR-T 치료라는것은 결국 환자의 면역세포 중의 하나인 T-cell을 추출하여 이들이 암세포를 인식하도록 수용체를 가공한 후에 다시 환자 몸에 넣어서 암세포만을 공격하도록하는 치료를 말한다.
CAR-T 적응증 및 가격
CAR-T의 선두주자는 노바티스(Novartis)사의 킴리아(KYMRIAH, tisagenlecleucel)인데, 재발성 혹은 불응성의 급성 림프구성 백혈병(Acute lymphoblastic leukemia)과 미만성 거대 B세포 림프종 (Diffuse large B-cell lymphoma)에서 허가가 되어있다.
킴리아는 1회 투여 가격이 3억6천만원의 초고가로 알려져 논란이 있었지만, 다행히도 2022년 4월부터 건강보험 급여가 적용되어 최대 598만원까지 환자 본인부담금이 낮아지게 되어 해당 질환을 앓고있는 환자들이 혜택을 보게 되었다. 또한, 이 치료제는 1회 치료로 완치되는 환자가 많다고 한다.
CAR-T 치료는 혈액암에는 잘듣지만 고형암에는 효과가 떨어지는 한계가 있다. 고형암에는 면역억제 미세환경이 존재하며, 혈관과 종양을 구성하는 섬유조직 때문에 CAR-T세포가 종양세포에 접근하기 어려운 경우가 많기 때문이다. 또한 종양으로 침투하더라도 다양한 면역억제 기작에 의해 T세포들이 제대로 역할을 하지 못하는 경우가 많다.
CAR-T는 또한 주입된 세포로 인해 염증반응이 촉발, 전신의 백혈구가 활성화되면 염증성 사이토카인이 과분비되는 사이토카인방출 증후군(cytokine release syndrome) 등의 부작용이 생길 수 있다.
CAR-T를 넘어서 CAR-NK
이러한 여러가지 CAR-T의 한계를 뛰어넘기 위해 제약업계에서는 최근 CAR-NK치료제를 개발하고 있다. CAR-NK는 chimeric antigen receptor NK-cell의 약자로, T세포 대신 NK세포(Natural killer cell, 자연살해세포)를 사용한 것이 특징이다. NK세포는 우리 몸의 선천면역세포로 체내에 있는 암세포, 바이러스에 감염된 세포, 변형된 세포 등 나쁜 세포라고 인식하면 즉각반응하는 특징을 가진다.
CAR-NK는 CAR-T세포의 부작용인 사이토카인방출증후군이나 신경독성 등이 적은 것으로 알려져 있다. 또한, CAR-T는 환자 본인의 T-cell을 추출하여 가공한 후 다시 넣어주는 복잡한 과정을 거쳐야하는데, CAR-NK의 경우에는 동종NK세포를 이용할 수 있다는 장점이 있다. 여기서, 동종 세포는 환자와의 HLA(인간백혈구항원)가 일치하지 않는 세포를 말하는데, T 세포의 경우에는 동종 세포를 사용할 경우 심각한 거부반응인 이식편대숙주병이 생기지만 NK세포의 경우에는 이것이 심하지 않을뿐만 아니라 자가세포에 비해 항암효능이 강한 것으로 알려져 있다.
지씨셀
국내에서 CAR-NK를 개발하고 있는 대표적인 회사는 지씨셀(144510)이다. 지씨셀은 세포치료제 분야에서 전문화된 기업으로, 암 치료제 개발을 중심으로 다양한 연구를 진행하고 있다. 최근에는 면역세포치료제 개발에 집중하며, CAR-T 세포치료제를 바탕으로 한 혁신적인 치료제를 개발하는 데 주력하고 있다. 모기업이 GC녹십자이며, 코스닥에 상장되어 있다. CAR-NK 파이프라인인 ‘AB101’은 2023년 말 임상1상이 종료될 예정이다.
AB101을 포함한 지씨셀 파이프라인 들의 내년 임상결과 발표 이벤트가 예정되어 있기 때문에 조정받은 현재 매수하는 것이 유효한 전략일 것으로 생각된다.
암세포를 타겟하는 똑똑한 치료제네요~
맞아요. 갈수록 치료제들이 똑똑해져 가는걸 느낍니다.^^
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