T lymphocytes engineered to express a CD16-chimeric antigen receptor redirect T-cell immune responses against immunoglobulin G–opsonized target cells

D’Aloia, Maria Michela; Caratelli, Sara; Palumbo, Camilla; Battella, Simone; Arriga, Roberto; Lauro, Davide; Palmieri, Gabriella; Sconocchia, Giuseppe; Alimandi, Maurizio

doi:10.1016/j.jcyt.2015.10.014

Cited by 48 publications

(58 citation statements)

References 55 publications

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“…Another class of receptor-based CARs makes use of the extracellular binding region of FcyRIII (CD16), which can be expressed in the surface of several immune cells, including monocytes, neutrophils, macrophages and NK cells [34, 35], This receptor mediates antibody-dependent cellular cytotoxicity (ADCC) through binding to Fc region of antibodies, therefore enhancing the effects of therapeutic antibodies regardless of the target tumor antigen. The ability of CD16 to bind IgG antibodies results in a potential universal CAR, where only one type of engineered T cells is needed to treat multiple types of cancer when given with the appropriate IgG antibodies that target that cancer.…”

Section: Natural Receptor-based Carsmentioning

confidence: 99%

Advances in the use of natural receptor- or ligand-based chimeric antigen receptors (CARs) in haematologic malignancies

Murad

Graber

Sentman

2018

Best Practice & Research Clinical Haematology

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Chimeric antigen receptors (CAR)-T cell therapy has recently made promising advances towards treatment of B-cell malignancies. This approach makes use of an antibody-derived single chain variable fragment (scFv)-based CAR to target the CD19 antigen. Currently scFvs are the most common strategy for creation of CARs, but tumor cells can also be targeted using non-antibody based approaches with designs focused on the interaction between natural receptors and their ligands. This emerging strategy has been used in unique ways to target multiple tumor types, including solid and haematological malignancies. In this review, we will highlight the performance of receptor-ligand combinations as designs for CARs to treat cancer, with a particular focus on haematologic malignancies.

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Section: Natural Receptor-based Carsmentioning

confidence: 99%

Advances in the use of natural receptor- or ligand-based chimeric antigen receptors (CARs) in haematologic malignancies

Murad

Graber

Sentman

2018

Best Practice & Research Clinical Haematology

View full text Add to dashboard Cite

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“…Two generations of CD16-CRs have been reported (35–38) (Figure 1). T cells transduced with CD16-CR display antitumor activity only when they are combined with mAbs.…”

Section: Cd16-crsmentioning

confidence: 99%

“…The second generation of CD16-CR was described both by Kudo et al (37) and by D’Aloia et al (38). Kudo et al generated the CD16V-BB-ζ-CR by introducing the TM portion of CD8a and the co-stimulatory endodomain of the 4-1BB into the module of the first-generation CD16ζ-CR (37).…”

Section: Second Generation Of Cd16-crmentioning

confidence: 99%

“…While Kudo et al highlighted the ADCC-mediated antitumor efficacy of the CD16-CR with the co-stimulatory domain of 4-1BB, D’Aloia et al investigated the ability of a CD16-CR variant carrying the CD28 co-stimulatory motif (CD16-28-ζ) (38). They assessed the functionality of the CD16-CR in the MD45 cell line, a murine T cell hybridoma lacking the lytic granule machinery but with cell killing ability through the Fas/FasL pathway.…”

Section: Second Generation Of Cd16-crmentioning

confidence: 99%

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FCγ Chimeric Receptor-Engineered T Cells: Methodology, Advantages, Limitations, and Clinical Relevance

et al. 2017

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For many years, disappointing results have been generated by many investigations, which have utilized a variety of immunologic strategies to enhance the ability of a patient’s immune system to recognize and eliminate malignant cells. However, in recent years, immunotherapy has been used successfully for the treatment of hematologic and solid malignancies. The impressive clinical responses observed in many types of cancer have convinced even the most skeptical clinical oncologists that a patient’s immune system can recognize and reject his tumor if appropriate strategies are implemented. The success immunotherapy is due to the development of at least three therapeutic strategies. They include tumor-associated antigen (TAA)-specific monoclonal antibodies (mAbs), T cell checkpoint blockade, and TAA-specific chimeric antigen receptors (CARs) T cell-based immunotherapy. However, the full realization of the therapeutic potential of these approaches requires the development of strategies to counteract and overcome some limitations. They include off-target toxicity and mechanisms of cancer immune evasion, which obstacle the successful clinical application of mAbs and CAR T cell-based immunotherapies. Thus, we and others have developed the Fc gamma chimeric receptors (Fcγ-CRs)-based strategy. Like CARs, Fcγ-CRs are composed of an intracellular tail resulting from the fusion of a co-stimulatory molecule with the T cell receptor ζ chain. In contrast, the extracellular CAR single-chain variable fragment (scFv), which recognizes the targeted TAA, has been replaced with the extracellular portion of the FcγRIIIA (CD16). Fcγ-CR T cells have a few intriguing features. First, given in combination with mAbs, Fcγ-CR T cells mediate anticancer activity in vitro and in vivo by an antibody-mediated cellular cytotoxicity mechanism. Second, CD16-CR T cells can target multiple cancer types provided that TAA-specific mAbs with the appropriate specificity are available. Third, the off-target effect of CD16-CR T cells may be controlled by withdrawing the mAb administration. The goal of this manuscript was threefold. First, we review the current state-of-the-art of preclinical CD16-CR T cell technology. Second, we describe its in vitro and in vivo antitumor activity. Finally, we compare the advantages and limitations of the CD16-CR T cell technology with those of CAR T cell methodology.

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“…Approximately 40% of people are known to carry the F158V polymorphism in CD16a, which significantly increases the affinity of this receptor to antibodies [41, 42]. The use of the extracellular domain of this receptor as the antigen-recognition domain made it possible to design uCARs that can re-target the cytotoxic activity of T cells according to the antitumor antibodies being infused [43-45]. This approach is potentially complicated by the presence of an excess of free antibodies present in the serum that may outcompete the administered mAbs in binding to CD16-CAR T cells.…”

Section: The Antigen-recognition Domain Of Carmentioning

confidence: 99%

Engineering Chimeric Antigen Receptors

et al. 2017

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Chimeric antigen receptors (CARs) are recombinant protein molecules that redirect cytotoxic lymphocytes toward malignant and other target cells. The high feasibility of manufacturing CAR-modified lymphocytes for the therapy of cancer has spurred the development and optimization of new CAR T cells directed against a broad range of target antigens. In this review, we describe the main structural and functional elements constituting a CAR, discuss the roles of these elements in modulating the anti-tumor activity of CAR T cells, and highlight alternative approaches to CAR engineering.

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T lymphocytes engineered to express a CD16-chimeric antigen receptor redirect T-cell immune responses against immunoglobulin G–opsonized target cells

Cited by 48 publications

References 55 publications

Advances in the use of natural receptor- or ligand-based chimeric antigen receptors (CARs) in haematologic malignancies

Advances in the use of natural receptor- or ligand-based chimeric antigen receptors (CARs) in haematologic malignancies

FCγ Chimeric Receptor-Engineered T Cells: Methodology, Advantages, Limitations, and Clinical Relevance

Engineering Chimeric Antigen Receptors

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