Retracted: Antitumor activity of human γδ T cells transducted with CD8 and with T‐cell receptors of tumor‐specific cytotoxic T lymphocytes

Abstract

The difficulty in the induction and preparation of a large number of autologous tumor-specific cytotoxic T lymphocytes (CTL) from individual patients is one of major problems in their application to adoptive immunotherapy. The present study tried to establish the useful antitumor effectors by using cd T cells through tumorspecific TCRab genes transduction, and evaluated the efficacy of their adoptive transfer in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice model. The TCRab gene was cloned from the HLA-B15-restricted CTL clone specific of the KitaKyushu Lung Cancer antigen-1 (KK-LC-1). The cloned TCRab as well as the CD8 gene were transduced into cd T cells induced from peripheral blood lymphocytes (PBL). Cytotoxic T lymphocyte activity was examined using a standard 4 h L ung cancer is the most common malignant neoplasm and the leading cause of cancer mortality in industrialized countries.(1) In spite of advances in diagnostic and therapeutic approaches against lung cancer, there has been limited improvement in treatment outcome. Recent clinical studies on immunotherapy indicate favorable therapeutic effects, and might become one of the alternative treatment approaches for lung cancer.(2-4) The adoptive transfer of tumor-infiltrating lymphocytes after the administration of lymphodepleting preparative regimen mediates objective cancer regression in 50% of patients with metastatic melanoma.(5) However, the difficulty in the induction and expansion of a large number of autologous tumor-specific cytotoxic T lymphocytes (CTL) from individual patients is one of the major problems in their application to adoptive immunotherapy. To overcome this drawback, T-cell receptors (TCR) can be harnessed with antitumor specificities via molecular techniques. T-cell receptors with known antitumor reactivity can be genetically introduced into primary human T lymphocytes and provide effective tools for immunogenic therapy of tumors. (6) In contrast, human cd T cells can recognize and respond to a wide variety of stress-induced antigens, thereby developing innate broad antitumor and anti-infective activity.(7) These cells recognize antigens in a HLA complex-independent manner and develop strong cytolytic and Th1-like effector functions.(7) Furthermore, human cd T cells can be activated by phospho-antigens and aminobisphosphonates. Aminobisphosphonates also facilitate large-scale ex vivo expansion of functional cd T cells from the peripheral blood of cancer patients.(8) Although the antitumor effect is not antigen-specific cytotoxicity, cd T cells are attractive candidate effector cells for cancer immunotherapy.Kita-Kyushu Lung Cancer antigen-1 (KK-LC-1) is a recently identified cancer/testis (CT) antigen from lung adenocarcinoma.(9) KK-LC-1 is a cancer/testis antigen because it is not expressed in normal tissues except for the testis, and is located on the X chromosome (Xq 22). A 9-mer peptide (KK-LC-1 76-84 ; RQKRILVNL) is recognized by CTL in a HLA B15-restricted manner. The present study tried to establish ...

Human Adenovirus-Specific γ/δ and CD8+ T Cells Generated by T-Cell Receptor Transfection to Treat Adenovirus Infection after Allogeneic Stem Cell Transplantation

“…It was shown that γ/δ T cells – retrovirally transfected with α/β TCR against e.g. CMV or a tumor antigen- were highly functional in vitro [23] and in mice [24] , [25] .…”

Adoptive immunotherapy shows encouraging benefit on non-small cell lung cancer: a systematic review and meta-analysis

“…Antibody-expanded γδ T cells generating more effector T cells may release greater amounts of cytokine, and may immediately induce cytotoxicity functions [ 29 ]. Hanagiri [ 30 ] et al stated that, when γδ T cells expressed specific αβ TCR molecules in addition to γδ TCR, they were more effective in NSCLC patients. NK are the innate effector cells of immune response to pathogens and cancer.…”

Trial Watch

“…The results of these studies are highly relevant for the development of novel ACT strategies that exert superior antineoplastic activity. Along similar lines, the discovery that γδ T cells also mediate potent antitumor effects upon re-infusion (following “conventional” expansion/activation only or in combination with the retroviral transduction of CD8 plus a tumor-reactive αβ TCR) paves an interesting avenue for the development of innovative ACT protocols 128 - 131 …”