Promising Cell-Based Immunotherapy Using Gamma Delta T Cells: Together Is Better

Déchanet‐Merville, Julie

doi:10.1158/1078-0432.ccr-14-1371

Cited by 4 publications

(2 citation statements)

References 10 publications

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“…Highly polyclonal γδ T cells have been generated through co-culture of patient or healthy donor γδ T cells with irradiated artificial antigen presenting cells (aAPC), IL-2, and IL-21 ( 77 – 80 ). The aAPC (clone#4) are derived from the chronic myelogenous leukemia (CML) cell line K562 following genetic modification with T-cell co-stimulatory molecules (CD86 and CD137L), Fc receptors for antibody loading (introduced CD64 and endogenous CD32), antigens (CD19), and cytokines (a membrane-bound IL-15), and have been produced as a master cell bank (MCB) ( 81 ).…”

Section: Ex Vivo Propagation Of Non-vγ9vδ2 γδ T Cellsmentioning

confidence: 99%

Clinical Applications of Gamma Delta T Cells with Multivalent Immunity

2014

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γδ T cells hold promise for adoptive immunotherapy because of their reactivity to bacteria, viruses, and tumors. However, these cells represent a small fraction (1–5%) of the peripheral T-cell pool and require activation and propagation to achieve clinical benefit. Aminobisphosphonates specifically expand the Vγ9Vδ2 subset of γδ T cells and have been used in clinical trials of cancer where objective responses were detected. The Vγ9Vδ2 T cell receptor (TCR) heterodimer binds multiple ligands and results in a multivalent attack by a monoclonal T cell population. Alternatively, populations of γδ T cells with oligoclonal or polyclonal TCR repertoire could be infused for broad-range specificity. However, this goal has been restricted by a lack of applicable expansion protocols for non-Vγ9Vδ2 cells. Recent advances using immobilized antigens, agonistic monoclonal antibodies (mAbs), tumor-derived artificial antigen presenting cells (aAPC), or combinations of activating mAbs and aAPC have been successful in expanding gamma delta T cells with oligoclonal or polyclonal TCR repertoires. Immobilized major histocompatibility complex Class-I chain-related A was a stimulus for γδ T cells expressing TCRδ1 isotypes, and plate-bound activating antibodies have expanded Vδ1 and Vδ2 cells ex vivo. Clinically sufficient quantities of TCRδ1, TCRδ2, and TCRδ1negTCRδ2neg have been produced following co-culture on aAPC, and these subsets displayed differences in memory phenotype and reactivity to tumors in vitro and in vivo. Gamma delta T cells are also amenable to genetic modification as evidenced by introduction of αβ TCRs, chimeric antigen receptors, and drug-resistance genes. This represents a promising future for the clinical application of oligoclonal or polyclonal γδ T cells in autologous and allogeneic settings that builds on current trials testing the safety and efficacy of Vγ9Vδ2 T cells.

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Section: Ex Vivo Propagation Of Non-vγ9vδ2 γδ T Cellsmentioning

confidence: 99%

Clinical Applications of Gamma Delta T Cells with Multivalent Immunity

2014

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“…Thus, for example, mounting evidence indicates that myeloidderived suppressor cells (MDSCs) (1) are important in tumor evasion and are negatively associated with the clinical course in several cancer entities (2)(3)(4). Many other cells are also involved in immune responses to tumors, mediating both anti-and procancer effects, including ab T cells (2,5,6), gd T cells (7), NK cells (8) and B cells (9). Here, we aimed to identify informative signatures by simultaneous analysis of all these immune cell types.…”

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confidence: 99%

Establishing High Dimensional Immune Signatures from Peripheral Blood via Mass Cytometry in a Discovery Cohort of Stage IV Melanoma Patients

Wistuba‐Hamprecht

Martens

Weide

et al. 2017

The Journal of Immunology

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The identification of blood-borne biomarkers correlating with melanoma patient survival remains elusive. Novel techniques such as mass cytometry could help to identify melanoma biomarkers, allowing simultaneous detection of up to 100 parameters. However, the evaluation of multiparametric data generated via time-of-flight mass cytometry requires novel analytical techniques because the application of conventional gating strategies currently used in polychromatic flow cytometry is not feasible. In this study, we have employed 38-channel time-of-flight mass cytometry analysis to generate comprehensive immune cell signatures using matrix boolean analysis in a cohort of 28 stage IV melanoma patients and 17 controls. Clusters of parameters were constructed from the abundance of cellular phenotypes significantly different between patients and controls. This approach identified patient-specific combinatorial immune signatures consisting of high-resolution subsets of the T cell, NK cell, B cell, and myeloid compartments. An association with superior survival was characterized by a balanced distribution of myeloid-derived suppressor cell-like and APC-like myeloid phenotypes and differentiated NK cells. The results of this study in a discovery cohort of melanoma patients suggest that multifactorial immune signatures have the potential to allow more accurate prediction of individual patient outcome. Further investigation of the identified immune signatures in a validation cohort is now warranted.

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Cell‐Based Cancer Immunotherapy

Patel

Moyes

Cooper

2017

Holland‐Frei Cancer Medicine

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Overview For decades, scientists have applied cell‐based immunotherapies for treatment of cancers. The successful administration of polyclonal populations of donor‐derived or autologous T cells is based in part on defining the precise cellular effectors and identifying tumor‐associated antigens (TAAs) that can be targeted to safely achieve an antitumor effect without engendering on‐target, but off‐tissue toxicity, such as manifested by graft‐versus‐host‐disease (GvHD). The adoptive transfer of T cells can reconstitute or enhance resident immunity, which is in contrast to the apparent limitations associated with vaccine‐based strategies in recipients whose endogenous immune system may fail to respond to immunogen. Other cytolytic circulating lymphocyte populations can be harnessed for infusion. These include allogeneic NK cells that may mediate an antitumor effect without a priori defining the TAA and perhaps without the risk of GvHD. In some cases, a TAA can be identified, for example, the B‐lineage TAA CD19, but host immune tolerance prevents the emergence of an effective immune response. Genetic engineering has been combined with T‐cell therapy to generate antigen‐specific cells ex vivo , through the enforced expression of chimeric antigen receptors (CARs). The adoptive transfer of CD19‐specific CAR + T cells has shown promise in initial clinical trials for successful disease control in patients with B‐cell malignancies resistant to conventional therapeutic modalities. Here, we describe the current status of cell‐based immunotherapy for cancer.

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Promising Cell-Based Immunotherapy Using Gamma Delta T Cells: Together Is Better

Cited by 4 publications

References 10 publications

Clinical Applications of Gamma Delta T Cells with Multivalent Immunity

Clinical Applications of Gamma Delta T Cells with Multivalent Immunity

Establishing High Dimensional Immune Signatures from Peripheral Blood via Mass Cytometry in a Discovery Cohort of Stage IV Melanoma Patients

Cell‐Based Cancer Immunotherapy

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