Anti-CD20 antibody-monomethyl auristatin E conjugate, preparation method and application thereof

A technology of dolastatin and conjugates, applied in the fields of biotechnology and medicine, can solve problems such as cell damage, reduce toxic side effects, and enhance anti-tumor effects
CN103145847BActive Publication Date: 2014-05-21ZHEJIANG UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
ZHEJIANG UNIV
Publication Date
2014-05-21

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Abstract

The invention discloses an anti-CD20 antibody-monomethyl auristatin E (MMAE) conjugate, its preparation method and application. The anti-CD20 antibody-monomethyl auristatin E conjugate is formed by coupling of monomethyl auristatin E to the anti-CD20 antibody through a linking arm. Specifically, the light chain amino acid sequence of the anti-CD20 antibody is shown as SEQ ID No.1, and its heavy chain amino acid sequence is shown as SEQ ID No.2. The anti-CD20 antibody-monomethyl auristatin E conjugate can be applied in preparation of antitumor drugs. The conjugate provided in the invention has the biological functions of resisting both the CD20 antibody and MMAE, and under cooperation of the two, the anti-tumor effect can be significantly enhanced.
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Description

technical field

[0001] The invention belongs to the fields of biotechnology and medicine, and in particular relates to an anti-CD20 antibody-dolastatin conjugate and a preparation method and application thereof. Background technique

[0002] CD20 is a unique membrane surface protein on the surface of B lymphocytes and B lymphoma cells, which is not expressed in hematopoietic stem cells, primitive B cells, normal plasma cells and other normal tissues (Bubien J K et al., J Cell Biol, 1993, 121 (5): 1121-1132). Therefore, the development of monoclonal antibodies against CD20 antigen can specifically kill B cells and B lymphoma cells and achieve good therapeutic effects.

[0003] Ofatumumab (2F2) is a fully humanized targeting anti-CD20 monoclonal antibody, which was approved by the FDA in 2009 for refractory chronic lymphocytic leukemia (CLL) ineffective in the treatment of fludarabine and alemtuzumab (CASTILLO J. Expert Opin Investing Drμgs, 2009, 18(4):491-500.). 2F2 binds...

Claims

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