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Next Article 
Blood, 1 December 2000, Vol. 96, No. 12, pp. 3663-3670
PLENARY PAPER
Enhanced antitumor immunity by fusion of CTLA-4 to a self
tumor antigen
Tzu-Hsuan Huang,
Pin-Yi Wu,
Chin-Nien Lee,
Hsing-I Huang,
Shie-Liang Hsieh,
John Kung, and
Mi-Hua Tao
From the Institute of Biomedical Sciences, Academia
Sinica, Taipei, Taiwan; Graduate Institute of Medical Technology,
National Taiwan University, Taipei, Taiwan; Department of Microbiology
and Immunology, National Yang-Ming University, Taipei, Taiwan; and
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
The idiotypic determinant (Id) of the immunoglobulin expressed by a
B-cell malignancy can serve as an effective tumor-specific antigen but
is only weakly immunogenic. This study demonstrates that the
immunogenicity of the tumor Id protein can be dramatically increased by
directing it to antigen-presenting cells (APCs). Cytotoxic T-lymphocyte
antigen 4 (CTLA-4) present on activated T cells has a strong binding
affinity to both B7-1 and B7-2 molecules, which are primarily expressed
on APCs. After construction of a fusion protein consisting of Id and
CTLA-4 (Id-CTLA4), mice immunized with the fusion protein induced high
titers of Id-specific antibody and T-cell proliferative responses
without adjuvants and were protected from lethal tumor challenge. The
Id-CTLA4 fusion protein was so potent that even low doses (down to 0.1 µg) of the immunogen were able to elicit strong antibody responses.
By using an Id-CTLA4 mutant protein, the ability to bind B7 molecules
on APCs was shown to be required for the enhanced immunogenicity of
Id-CTLA4. These findings demonstrate that fusing CTLA-4 to a potential
tumor antigen represents an effective approach to prime
antitumor immunities in vivo and may be applicable to
the design of vaccines for a variety of other diseases.
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