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Antiproliferative and Apoptotic Effects of Novel Anti-ROR1 Single-Chain Antibodies in Hematological Malignancies.
SLAS Discov 2017; 22(4):408-417SD

Abstract

Receptor tyrosine kinase-like orphan receptor (ROR) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including cell survival, differentiation, cell migration, cell communication, cell polarity, proliferation, metabolism, and angiogenesis. ROR1 has recently been shown to be expressed in various types of cancer cells but not normal cells. Pharmacokinetics and pharmacodynamics of single-chain Fragment variable (scFv) antibodies provide potential therapeutic advantages over whole antibody molecules. In the present study, scFvs against a specific peptide from the extracellular domain of ROR1 were selected using phage display technology. The selected scFvs were further characterized using polyclonal and monoclonal phage enzyme-linked immunosorbent assay (ELISA), soluble monoclonal ELISA, colony PCR, and sequencing. Antiproliferative and apoptotic effects of selected scFv antibodies were also evaluated in lymphoma and myeloma cancer cell lines using MTT and annexin V/PI assays. The results of ELISA indicated specific reactions of the isolated scFvs against the ROR1 peptide. Colony PCR confirmed the presence of full-length VH and Vκ inserts. The percentages of cell growth after 24 h of treatment of cells with individual scFv revealed that the scFv significantly inhibited the growth of the RPMI8226 and chronic lymphocytic leukemia (CLL) cells in comparison with the untreated cells (p < 0.05). Interestingly, 24-h treatment with specific scFv induced apoptosis cell death in the RPMI8226 and CLL cells. Taken together, our results demonstrate that targeting of ROR1 using peptide-specific scFv can be an effective immunotherapy strategy in hematological malignancies.

Authors+Show Affiliations

1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 3 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. 4 Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.5 Faculty of Paramedical Sciences, Alborz University of Medical Sciences, Karaj, Iran. 6 Pishtaz Teb Zaman Diagnostics, Tehran, Iran.1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 4 Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 4 Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 4 Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 4 Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 4 Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28328317

Citation

Aghebati-Maleki, Leili, et al. "Antiproliferative and Apoptotic Effects of Novel Anti-ROR1 Single-Chain Antibodies in Hematological Malignancies." SLAS Discovery : Advancing Life Sciences R & D, vol. 22, no. 4, 2017, pp. 408-417.
Aghebati-Maleki L, Younesi V, Baradaran B, et al. Antiproliferative and Apoptotic Effects of Novel Anti-ROR1 Single-Chain Antibodies in Hematological Malignancies. SLAS Discov. 2017;22(4):408-417.
Aghebati-Maleki, L., Younesi, V., Baradaran, B., Abdolalizadeh, J., Motallebnezhad, M., Nickho, H., ... Yousefi, M. (2017). Antiproliferative and Apoptotic Effects of Novel Anti-ROR1 Single-Chain Antibodies in Hematological Malignancies. SLAS Discovery : Advancing Life Sciences R & D, 22(4), pp. 408-417. doi:10.1177/2472555216689659.
Aghebati-Maleki L, et al. Antiproliferative and Apoptotic Effects of Novel Anti-ROR1 Single-Chain Antibodies in Hematological Malignancies. SLAS Discov. 2017;22(4):408-417. PubMed PMID: 28328317.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antiproliferative and Apoptotic Effects of Novel Anti-ROR1 Single-Chain Antibodies in Hematological Malignancies. AU - Aghebati-Maleki,Leili, AU - Younesi,Vahid, AU - Baradaran,Behzad, AU - Abdolalizadeh,Jalal, AU - Motallebnezhad,Morteza, AU - Nickho,Hamid, AU - Shanehbandi,Dariush, AU - Majidi,Jafar, AU - Yousefi,Mehdi, Y1 - 2017/01/31/ PY - 2017/3/23/entrez PY - 2017/3/23/pubmed PY - 2019/1/17/medline KW - ROR1 KW - hematological malignancies KW - immunotherapy KW - phage display KW - scFv SP - 408 EP - 417 JF - SLAS discovery : advancing life sciences R & D JO - SLAS Discov VL - 22 IS - 4 N2 - Receptor tyrosine kinase-like orphan receptor (ROR) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including cell survival, differentiation, cell migration, cell communication, cell polarity, proliferation, metabolism, and angiogenesis. ROR1 has recently been shown to be expressed in various types of cancer cells but not normal cells. Pharmacokinetics and pharmacodynamics of single-chain Fragment variable (scFv) antibodies provide potential therapeutic advantages over whole antibody molecules. In the present study, scFvs against a specific peptide from the extracellular domain of ROR1 were selected using phage display technology. The selected scFvs were further characterized using polyclonal and monoclonal phage enzyme-linked immunosorbent assay (ELISA), soluble monoclonal ELISA, colony PCR, and sequencing. Antiproliferative and apoptotic effects of selected scFv antibodies were also evaluated in lymphoma and myeloma cancer cell lines using MTT and annexin V/PI assays. The results of ELISA indicated specific reactions of the isolated scFvs against the ROR1 peptide. Colony PCR confirmed the presence of full-length VH and Vκ inserts. The percentages of cell growth after 24 h of treatment of cells with individual scFv revealed that the scFv significantly inhibited the growth of the RPMI8226 and chronic lymphocytic leukemia (CLL) cells in comparison with the untreated cells (p < 0.05). Interestingly, 24-h treatment with specific scFv induced apoptosis cell death in the RPMI8226 and CLL cells. Taken together, our results demonstrate that targeting of ROR1 using peptide-specific scFv can be an effective immunotherapy strategy in hematological malignancies. SN - 2472-5560 UR - https://www.unboundmedicine.com/medline/citation/28328317/Antiproliferative_and_Apoptotic_Effects_of_Novel_Anti_ROR1_Single_Chain_Antibodies_in_Hematological_Malignancies_ L2 - http://journals.sagepub.com/doi/full/10.1177/2472555216689659?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -