In Vitro and In Vivo Characterization of a Novel Antibody-Like Single-Chain TCR Human IgG1 Fusion Protein | Zendy

Luis A. Mosquera | Zendy; Kimberlyn F. Card | Zendy; Shari A. PriceSchiavi | Zendy; Heather J. Belmont | Zendy; Bai Liu | Zendy; Janette Builes | Zendy; Xiaoyun Zhu | Zendy; PierreAndré Chavaillaz | Zendy; Hyungil Lee | Zendy; Jinan Jiao | Zendy; John L. Francis | Zendy; Ali Amirkhosravi | Zendy; Richard Wong | Zendy; Hing C. Wong | Zendy

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In Vitro and In Vivo Characterization of a Novel Antibody-Like Single-Chain TCR Human IgG1 Fusion Protein

Author(s) -

Luis A. Mosquera,

Kimberlyn F. Card,

Shari A. PriceSchiavi,

Heather J. Belmont,

Bai Liu,

Janette Builes,

Xiaoyun Zhu,

PierreAndré Chavaillaz,

Hyungil Lee,

Jinan Jiao,

John L. Francis,

Ali Amirkhosravi,

Richard Wong,

Hing C. Wong

Publication year - 2005

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.174.7.4381

Subject(s) - fusion protein , effector , context (archaeology) , t cell receptor , in vivo , in vitro , cytotoxicity , biology , microbiology and biotechnology , antibody , immunoglobulin light chain , peptide , t cell , computational biology , chemistry , biochemistry , immunology , recombinant dna , immune system , gene , genetics , paleontology

We have constructed a protein composed of a soluble single-chain TCR genetically linked to the constant domain of an IgG1 H chain. The Ag recognition portion of the protein binds to an unmutated peptide derived from human p53 (aa 264-272) presented in the context of HLA-A2.1, whereas the IgG1 H chain provides effector functions. The protein is capable of forming dimers, specifically staining tumor cells and promoting target and effector cell conjugation. The protein also has potent antitumor effects in an in vivo tumor model and can mediate cell killing by Ab-dependent cellular cytotoxicity. Therefore, single-chain TCRs linked to IgG1 H chains behave like Abs but possess the ability to recognize Ags derived from intracellular targets. These fusion proteins represent a novel group of immunotherapeutics that have the potential to expand the range of tumors available for targeted therapies beyond those currently addressed by the conventional Ab-based approach.

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