2016
DOI: 10.18632/oncotarget.11785
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Has erratum 2018-8-17Has correction 2018-8-17
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Abstract: Redirection of T cells to target and destroy tumors has become an important clinical tool and major area of research in tumor immunology. Here we present a novel, nanoparticle-based approach to selectively bind antigen-specific cytotoxic T cells (CTL) and redirect them to kill tumors, termed ATR (Antigen-specific T cell Redirectors). ATR were generated by decorating nanoparticles with both an antigen-specific T cell binding moiety, either peptide loaded MHC-Ig dimer or clonotypic anti-TCR antibody, and a model… Show more

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Cited by 25 publications
(18 citation statements)
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References 42 publications
(35 reference statements)
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“…Using PLGA particles as an analog to BiTEs, Schütz et al showed that nanoparticles bi-functionalized with an antibody targeting a tumor cell surface antigen together with a peptide-MHC complex to target pre-existing memory T-cells could be used to redirect influenza-specific memory T-cells against lymphomas in a humanized mouse model [279]. This approach may have advantages relative to CD3-targeting BiTEs, by allowing specific memory T-cell populations to be targeted that could be selected for known favorable effector profiles (e.g., flu or CMV-specific T-cell populations).…”
Section: Engineering Safer Systemic Immunotherapiesmentioning
confidence: 99%
“…Using PLGA particles as an analog to BiTEs, Schütz et al showed that nanoparticles bi-functionalized with an antibody targeting a tumor cell surface antigen together with a peptide-MHC complex to target pre-existing memory T-cells could be used to redirect influenza-specific memory T-cells against lymphomas in a humanized mouse model [279]. This approach may have advantages relative to CD3-targeting BiTEs, by allowing specific memory T-cell populations to be targeted that could be selected for known favorable effector profiles (e.g., flu or CMV-specific T-cell populations).…”
Section: Engineering Safer Systemic Immunotherapiesmentioning
confidence: 99%
“…Future studies investigating the impact of core scaffold size and targeted cytokine neutralization, rather than delivery, may also lead to further improvements in BiTEokine activity or an expansion of disease targets, respectively. While a limited number of promising synthetic P r e p r i n t C o p y ICR agents have been previously described, [9][10][11] these studies are the first -to our knowledge -to present a method for the discovery and screening-based optimization of this promising class of immunotherapy. Given the rapid and modular nature of the approach presented here, we also anticipate facile extension to a wide range of immune cells, diseased cells, and soluble protein combinations in the future.…”
Section: Discussionmentioning
confidence: 99%
“…2 In addition to their diversity of application, ICR immunotherapies can also vary widely in their composition and mode of delivery. They encompass nanoparticle [9][10][11] , bispecific IgG, 12,13 scFv fusion, 14 and mRNA 15 constructs, as well as vectors based on oncolytic viruses 16 and engineered cells. 17 While a majority of ICR therapies in clinical testing are produced using traditional genetic engineering techniques, one challenge to their discovery and development is the relatively low-throughput manner in which drug candidates can be investigated and the relatively high dependency of drug action on the affinity of individual cell-binding domains.…”
Section: Introductionmentioning
confidence: 99%
“…In this approach, bacterial viruses had been used not only as phages conjugated with functionalized (with carboxyl and amino groups, respectively, for better loading) MONPs for antimicrobial purposes [103] but also as a scaffold to carry more Fe 2 O 3 NPs that can powerfully bind with cancer cell surfaces than Fe 2 O 3 NPs themselves [104]. Moreover, antibody and antibody-like conjugates to NPs can be bi-specific complexes with multiple modes of action including the delivery of toxins or agents that kill tumor cells; inhibition of two ligands or receptors; and crossing of two receptors [105]. However, there are many gaps in understanding the immune response that MONPs induce.…”
Section: Iron Oxides Nanoparticlesmentioning
confidence: 99%