Chuyển giao T tế bào đồng dạng được chuyển gen với thụ thể kháng nguyên tổng hợp nhận diện CD19 chuột có thể tiêu diệt lymphoma và tế bào B bình thường

Blood - Tập 116 - Trang 3875-3886 - 2010
James N. Kochenderfer1, Zhiya Yu1, Dorina Frasheri1, Nicholas P. Restifo1, Steven A. Rosenberg1
1Surgery Branch of the National Cancer Institute, National Institutes of Health, Bethesda, MD

Tóm tắt

Tóm tắtLiệu pháp T tế bào được nhận giao với các tế bào T biểu hiện thụ thể kháng nguyên tổng hợp (CAR) kháng CD19 là một phương pháp mới để điều trị các bệnh ác tính tế bào B tiên tiến. Để đánh giá các tế bào T chuyển gen anti-CD19–CAR trong một mô hình chuột của liệu pháp T tế bào nhận giao, chúng tôi đã phát triển một CAR nhận diện đặc hiệu CD19 chuột. Chúng tôi đã sử dụng các tế bào T được chuyển gen bằng retrovirus với CAR này để điều trị chuột mang lymphoma đồng hình tự nhiên biểu hiện tự kháng nguyên CD19 chuột. Một lần truyền tế bào T chuyển gen anti-CD19–CAR đã loại bỏ hoàn toàn các tế bào B bình thường khỏi chuột trong ít nhất 143 ngày. Tế bào T chuyển gen anti-CD19–CAR đã tiêu diệt các tế bào lymphoma được tiêm trong ổ bụng và các khối u lymphoma lớn dưới da. Hiệu quả chống lymphoma của tế bào T chuyển gen anti-CD19–CAR phụ thuộc rất nhiều vào việc chiếu xạ cho chuột trước khi truyền tế bào T chuyển gen anti-CD19–CAR. Tế bào T chuyển gen anti-CD19–CAR có hiệu quả chống lymphoma vượt trội so với kháng thể đơn dòng anti-CD19 từ đó CAR anti-CD19 được phát sinh. Các kết quả của chúng tôi đã chứng minh hoạt tính chống lymphoma ấn tượng và sự tiêu diệt sâu sắc các tế bào B bình thường do tế bào T chuyển gen anti-CD19–CAR gây ra trong một mô hình chuột có liên quan lâm sàng.

Từ khóa

#liệu pháp tế bào T #thụ thể kháng nguyên tổng hợp #CD19 #lymphoma #tế bào B bình thường #chuột.

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