Bispecific light T-cell engagers for gene-based immunotherapy of epidermal growth factor receptor (EGFR)-positive malignancies
| Autor: | Francisco J. Blanco, Marta Compte, Laura Sanz, Kasper Mølgaard, Nekane Merino, Kasper Mikkelsen, Natalia Nuñez-Prado, Ana María Álvarez-Méndez, Seandean Lykke Harwood, Ana Álvarez-Cienfuegos, Jaume Bonet, Luis Álvarez-Vallina |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research CD3 Complex T-Lymphocytes T cell medicine.medical_treatment Immunology Lymphocyte Activation 03 medical and health sciences Cancer immunotherapy Antigen Neoplasms Antibodies Bispecific Tumor Cells Cultured medicine Humans Immunology and Allergy Epidermal growth factor receptor Cell Proliferation biology Chemistry Immunotherapy ErbB Receptors Cytolysis 030104 developmental biology medicine.anatomical_structure Oncology Cancer cell Cancer research biology.protein Antibody Single-Chain Antibodies |
| Zdroj: | Jensen, K, Harwood, S L, Compte, M, Merino, N, Bonet, J, Álvarez-Cienfuegos, A, Mikkelsen, K, Alanes, N N D P, Álvarez-Méndez, A, Sanz, L, Blanco, F J & Álvarez-Vallina, L 2018, ' Bispecific light T-cell engagers for gene-based immunotherapy of epidermal growth factor receptor (EGFR)-positive malignancies ', Cancer Immunology, Immunotherapy, vol. 67, no. 8, pp. 1251-1260 . https://doi.org/10.1007/s00262-018-2181-5 |
| DOI: | 10.1007/s00262-018-2181-5 |
| Popis: | The recruitment of T-cells by bispecific antibodies secreted from adoptively transferred, gene-modified autologous cells has shown satisfactory results in preclinical cancer models. Even so, the approach’s translation into the clinic will require incremental improvements to its efficacy and reduction of its toxicity. Here, we characterized a tandem T-cell recruiting bispecific antibody intended to benefit gene-based immunotherapy approaches, which we call the light T-cell engager (LiTE), consisting of an EGFR-specific single-domain VHH antibody fused to a CD3-specific scFv. We generated two LiTEs with the anti-EGFR VHH and the anti-CD3 scFv arranged in both possible orders. Both constructs were well expressed in mammalian cells as highly homogenous monomers in solution with molecular weights of 43 and 41 kDa, respectively. In situ secreted LiTEs bound the cognate antigens of both parental antibodies and triggered the specific cytolysis of EGFR-expressing cancer cells without inducing T-cell activation and cytotoxicity spontaneously or against EGFR-negative cells. Light T-cell engagers are, therefore, suitable for future applications in gene-based immunotherapy approaches. |
| Databáze: | OpenAIRE |
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