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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
CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results
Chimeric antigen receptor (CAR) T cells targeting CD22 (CD22-CAR) provide a therapeutic option for patients with CD22+ malignancies with progression after CD19-directed therapies. Using on-site, automated, closed...
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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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Article
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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Article
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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Article
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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Article
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
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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Article
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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Article
Neuroblastoma
Neuroblastoma is the most common extracranial solid tumour occurring in childhood and has a diverse clinical presentation and course depending on the tumour biology. Unique features of these neuroendocrine tum...
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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
Antigen loading of DCs with irradiated apoptotic tumor cells induces improved anti-tumor immunity compared to other approaches
Dendritic cells (DCs) serve as central regulators of adaptive immunity by presenting antigens and providing necessary co-signals. Environmental information received by the DCs determines the co-signals deliver...
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Article
Immune reconstitution prevents metastatic recurrence of murine osteosarcoma
Primary tumors develo** in immunocompetent hosts escape immunosurveillance by acquiring immune evasive properties. This raises the prospect that metastases derived from such tumors will also evade immunity. ...
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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...