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Lee BS, Lee Y, Park J, et al. Construction of an immunotoxin via site-specific conjugation of anti-Her2 IgG and engineered . J Biol Eng. 2019;13:56doi: 10.1186/s13036-019-0188-x.
Lee, B. S., Lee, Y., Park, J., Jeong, B. S., Jo, M., Jung, S. T., & Yoo, T. H. (2019). Construction of an immunotoxin via site-specific conjugation of anti-Her2 IgG and engineered . Journal of biological engineering, 1356. https://doi.org/10.1186/s13036-019-0188-x
Lee, Byeong Sung, et al. "Construction of an immunotoxin via site-specific conjugation of anti-Her2 IgG and engineered ." Journal of biological engineering vol. 13 (2019): 56. doi: https://doi.org/10.1186/s13036-019-0188-x
Lee BS, Lee Y, Park J, Jeong BS, Jo M, Jung ST, Yoo TH. Construction of an immunotoxin via site-specific conjugation of anti-Her2 IgG and engineered . J Biol Eng. 2019 Jun 21;13:56. doi: 10.1186/s13036-019-0188-x. eCollection 2019. PMID: 31285754; PMCID: PMC6588878.
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J Biol Eng. 2019 Jun 21;13:56. doi: 10.1186/s13036-019-0188-x. eCollection 2019.

Construction of an immunotoxin via site-specific conjugation of anti-Her2 IgG and engineered .

Journal of biological engineering

Byeong Sung Lee, Yumi Lee, Jisoo Park, Bo Seok Jeong, Migyeong Jo, Sang Taek Jung, Tae Hyeon Yoo

Affiliations

  1. 1Department of Molecular Science and Technology, Ajou University, 206 World cup-ro, Yeongtong-gu, Suwon, 16499 South Korea.
  2. 3Department of Applied Chemistry, Kookmin University, 77 Jeongneung-ro, Seongbuk-gu, Seoul, 02707 South Korea.
  3. 4Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seongbuk-gu, Seoul, 02841 South Korea.
  4. 2Department of Applied Chemistry and Biological Engineering, Ajou University, 206 World cup-ro, Yeongtong-gu, Suwon, 16499 South Korea.

PMID: 31285754 PMCID: PMC6588878 DOI: 10.1186/s13036-019-0188-x

Abstract

BACKGROUND: Immunotoxins consisting of a toxin from bacteria or plants and a targeting module have been developed as potent anti-cancer therapeutics. The majority of them, especially those in preclinical or clinical testing stages, are fusion proteins of a toxin and antibody fragment. Immunotoxins based on full-length antibodies are less studied, even though the fragment crystallizable (Fc) domain plays an important role in regulating the concentration of immunoglobulin G (IgG) in the serum and in antibody-mediated immune responses against pathogens.

RESULTS: We devised a method to site-specifically conjugate IgG and another protein using a cysteine residue introduced into the IgG and a bio-orthogonally reactive unnatural amino acid incorporated into the other protein. The human epidermal growth factor receptor 2 (Her2)-targeting IgG, trastuzumab, was engineered to have an unpaired cysteine in the heavy chain, and an unnatural amino acid with the azido group was incorporated into an engineered

CONCLUSIONS: We constructed the site-specifically conjugated immunotoxin based on IgG and PE24, which induced target-specific cytotoxicity. To evaluate the molecule as a cancer therapeutic, animal studies are planned to assess tumor regression, half-life in blood, and in vivo immunogenicity. In addition, we expect that the site-specific conjugation method can be used to develop other antibody-protein conjugates for applications in therapeutics and diagnostics.

Keywords: Immunoglobulin G; Immunotoxin; Pseudomonas Exotoxin A; Site-specific conjugation; Unnatural amino acid

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

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