Cytokine-induced killer cells engineered with exogenous T-cell receptors directed against melanoma antigens: enhanced efficacy of effector cells endowed with a double mechanism of tumor recognition

Human Gene Therapy
Angela R EliaAlessandro Cignetti

Abstract

Cytokine-induced killer (CIK) cells consist of a heterogeneous population of polyclonal T lymphocytes displaying NK phenotype and HLA-unrestricted cytotoxic activity against a broad range of tumors. We sought to determine whether transduction of CIK cells with T cell receptor (TCR) genes specific for tumor-associated antigens could generate effector cells endowed with a double mechanism of tumor recognition. HLA-A2-restricted TCR-transduced (TD) CIK directed against the melanoma antigens Mart1 and NY-ESO1 were generated by lentiviral transduction and successfully expanded over a 3-4-week period. TD-CIK cells were both CD3(+)/CD56(-) and CD3(+)/CD56(+) (31±8% and 59±9%, respectively), indicating that both major histocompatibility complex (MHC)-restricted T cells and MHC-unrestricted CIK could be targeted by lentiviral transduction. At the end of the culture, the majority of both unmodified and TD-CIK displayed an effector memory phenotype, without considerable expression of replicative senescence and exhaustion markers. Functionally, TD-CIK specifically recognized tumor cells expressing the relevant antigen as well as maintained their MHC-unrestricted tumor activity. The cytotoxic activity of TD-CIK against HLA-A2(+) melanoma ce...Continue Reading

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Citations

May 4, 2018·Oncoimmunology·V LeuciD Sangiolo
Apr 11, 2018·Oncoimmunology·Paola CircostaGiorgio Inghirami
Nov 7, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Loretta GammaitoniDario Sangiolo
Jan 11, 2021·Pathology, Research and Practice·Jun XieLi Jin

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Methods Mentioned

BETA
xenograft
transfection
ELISA
density gradient centrifugation
flow cytometry
FACS
xenografts

Software Mentioned

Prism
GraphPad
CellQuest

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