Construction and characterization of a novel fusion protein consisting of anti-CD3 antibody fused to recombinant interleukin-2.

Kuan-Der Lee, Hsin-Wei Chen, Chih-Cheng Chen, Yan-Chung Shih, Hsing-Kun Liu, Mei-Lien Cheng

Department of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan. kdlee@adm.cgmh.org.tw

Oncology reports 2006 May

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T cells can be activated in vitro by monoclonal antibodies to CD3 (anti-CD3) to become non-MHC restricted killer cells (CD3-AK). Anti-CD3 activation upregulates the expression of the interleukin (IL)-2 receptors on T cells whose expansion is facilitated by IL-2. The therapeutic effect of in vivo administration of anti-CD3 and IL-2 has been investigated in many types of human cancers. To circumvent the toxicities posed by systemic administration of high-dose IL-2, there is interest in forming a strategy for targeting and concentrating IL-2 at the site where it is needed. This study investigates the feasibility of constructing a novel fusion protein consisting of IL-2 fused to the constant region of anti-CD3 antibody. Our results indicate that the specific IL-2 receptor-binding capability and bioactivity of the IL-2 portion as well as the CD3-binding and biological functions of anti-CD3 portion remain intact in this anti-CD3/IL-2 fusion protein. Thus, cytokines fused to anti-CD3 antibody by genetic engineering is feasible and may provide a new class of immunotherapeutics for cancer.

Citation

Kuan-Der Lee, Hsin-Wei Chen, Chih-Cheng Chen, Yan-Chung Shih, Hsing-Kun Liu, Mei-Lien Cheng. Construction and characterization of a novel fusion protein consisting of anti-CD3 antibody fused to recombinant interleukin-2. Oncology reports. 2006 May;15(5):1211-6