Kháng thể đơn dòng chống CCR7 như một công cụ mới trong điều trị bệnh bạch cầu lympho mãn tính
Tóm tắt
Tính đến nay, bệnh bạch cầu lympho mãn tính (CLL) vẫn chưa thể chữa khỏi bằng các phương pháp điều trị hiện tại, bao gồm các kháng thể đơn dòng (mAbs) rituximab và alemtuzumab. Hiệu quả của rituximab chỉ ở mức trung bình khi sử dụng như một tác nhân đơn lẻ, còn alemtuzumab gây ra suy giảm miễn dịch nghiêm trọng. Để phát triển các liệu pháp mạnh mẽ và đặc hiệu hơn, chúng tôi đề xuất thụ thể chemokine CC 7 (CCR7) như một phân tử mục tiêu hấp dẫn để điều trị CLL, vì nó không chỉ đáp ứng các yêu cầu về biểu hiện bề mặt cao và độ đặc hiệu mô tốt mà còn đóng vai trò quan trọng trong việc trung gian sự di chuyển của tế bào khối u đến hạch bạch huyết (LNs) và do đó, trong sự phát triển của hiện tượng hạch lympho lớn. Trong nghiên cứu hiện tại, kháng thể đơn dòng kháng CCR7 người chuột đã tạo ra một tác động độc tế bào phụ thuộc bổ thể (CDC) mạnh mẽ đối với các tế bào CLL trong khi bảo vệ các tế bào lympho T bình thường từ cùng một bệnh nhân. Độ nhạy đối với CDC có liên quan đến mật độ kháng nguyên của CCR7. Hơn nữa, các mAbs này đã chặn sự di chuyển in vitro của các tế bào CLL do phản ứng với ligand chemokine CC 19 (CC219), một trong những ligand sinh lý của CCR7. Ngược lại, các tế bào CLL không bị tiêu diệt hiệu quả thông qua độc tế bào trung gian kháng thể (ADCC), có thể là do nguồn gốc chuột và loại của mAbs kháng CCR7 được sử dụng. Các kỹ thuật kỹ thuật phân tử sẽ cho phép chúng tôi thu được kháng thể đơn dòng kháng CCR7 chimeric hoặc được nhân hóa để đạt được phản ứng lâm sàng tốt nhất cho loại bệnh bạch cầu phổ biến và vẫn chưa thể chữa trị này.
Từ khóa
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