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Article
Enhancing pediatric access to cell and gene therapies
Increasing numbers of cell and gene therapies (CGTs) are emerging to treat and cure pediatric diseases. However, small market sizes limit the potential return on investment within the traditional biopharmaceut...
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Article
Unanswered questions following reports of secondary malignancies after CAR-T cell therapy
Reports of T cell malignancies after CAR-T cell therapy should be investigated, but existing data from follow-up studies suggest a low risk compared with other cancer treatments.
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Open AccessHomology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing
Chimeric Antigen Receptor (CAR) T cells are now standard of care (SOC) for some patients with B cell and plasma cell malignancies and could disrupt the therapeutic landscape of solid tumors. However, access to...
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Tumor inflammation-associated neurotoxicity
Cancer immunotherapies have unique toxicities. Establishment of grading scales and standardized grade-based treatment algorithms for toxicity syndromes can improve the safety of these treatments, as observed f...
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Article
Post-infusion CAR TReg cells identify patients resistant to CD19-CAR therapy
Approximately 60% of patients with large B cell lymphoma treated with chimeric antigen receptor (CAR) T cell therapies targeting CD19 experience disease progression, and neurotoxicity remains a challenge. Biom...
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Article
Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication
The disialoganglioside GD2 is overexpressed on several solid tumors, and monoclonal antibodies targeting GD2 have substantially improved outcomes for children with high-risk neuroblastoma. However, approximate...
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Open AccessCAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial
Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL)...
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Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors
Atypical teratoid/rhabdoid tumors (ATRTs) typically arise in the central nervous system (CNS) of children under 3 years of age. Despite intensive multimodal therapy (surgery, chemotherapy and, if age permits, ...
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Article
Clinical lessons learned from the first leg of the CAR T cell journey
Chimeric antigen receptor (CAR) T cell therapy for B cell malignancies has surpassed expectations, driving an ever-expanding number of clinical trials and the first US Food and Drug Administration approvals of...
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Article
CAR T cell therapy: inroads to response and resistance
Here, we highlight key papers published in 2018 that advance our understanding of resistance to chimeric antigen receptor (CAR) T cell immunotherapy for leukaemia and lymphoma and in so doing reveal barriers t...
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Programming CAR-T cells to kill cancer
T cells engineered to express chimeric antigen receptors (CARs) that are specific for tumour antigens have led to high complete response rates in patients with haematologic malignancies. Despite this early suc...
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Article
Open AccessFludarabine and neurotoxicity in engineered T-cell therapy
Adoptive T-cell therapy, incorporating engineered T cell receptors (TCRs) or chimeric antigen receptors (CARs), target tumor antigens with high affinity and specificity. To increase the potency of adoptively t...
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Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline gliomas
Diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMGs) with mutated histone H3 K27M (H3-K27M)1–5 are aggressive and universally fatal pediatric brain cancers6. Chimeric antigen receptor ...
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CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy
Fry et al. report the first results from a human trial of a CD22-directed chimeric antigen receptor (CAR) T cell therapy providing evidence of efficacy in the treatment of pre–B cell acute lymphoblastic leukemia ...
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Open AccessElutriated lymphocytes for manufacturing chimeric antigen receptor T cells
Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, ...
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Article
4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors
Crystal Mackall and colleagues report that antigen-independent signaling of chimeric antigen receptors (CARs) causes T cell exhaustion and reduced therapeutic efficacy of CAR T cells that can be overcome by in...
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Article
Harnessing the biology of IL-7 for therapeutic application
Interleukin-7 (IL-7) is required for T cell development in mice and humans and is produced by stromal tissues rather than activated lymphocytes. Under normal c...
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Reply to “Is IL-7 from dendritic cells essential for the homeostasis of CD4+ T cells?”
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Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells
Compared with naive CD8+ T cells, naive CD4+ T cells undergo inefficient homeostatic proliferation. Mackall and colleagues now attribute this difference to interleukin 7–mediated suppression of the expression of ...
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Article
Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells
CD4+CD25+ regulatory T (Treg) cells have a crucial role in maintaining immune tolerance. Mice and humans born lacking Treg cells develop severe autoimmune disease1,2, and depletion of Treg cells in lymphopenic mi...