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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
Open AccessEngineered CD47 protects T cells for enhanced antitumour immunity
Adoptively transferred T cells and agents designed to block the CD47–SIRPα axis are promising cancer therapeutics that activate distinct arms of the immune system1,2. Here we administered anti-CD47 antibodies in ...
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Article
Targeting TGFβ-activated kinase-1 activation in microglia reduces CAR T immune effector cell-associated neurotoxicity syndrome
Cancer immunotherapy with chimeric antigen receptor (CAR) T cells can cause immune effector cell-associated neurotoxicity syndrome (ICANS). However, the molecular mechanisms leading to ICANS are not well under...
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Article
Open AccessPublisher Correction: FOXO1 is a master regulator of memory programming in CAR T cells
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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
Open AccessFOXO1 is a master regulator of memory programming in CAR T cells
A major limitation of chimeric antigen receptor (CAR) T cell therapies is the poor persistence of these cells in vivo1. The expression of memory-associated genes in CAR T cells is linked to their long-term persis...
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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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Author Correction: CAR immune cells: design principles, resistance and the next generation
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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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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
Co-opting signalling molecules enables logic-gated control of CAR T cells
Although chimeric antigen receptor (CAR) T cells have altered the treatment landscape for B cell malignancies, the risk of on-target, off-tumour toxicity has hampered their development for solid tumours becaus...
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Article
CAR immune cells: design principles, resistance and the next generation
The remarkable clinical activity of chimeric antigen receptor (CAR) therapies in B cell and plasma cell malignancies has validated the use of this therapeutic class for liquid cancers, but resistance and limit...
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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
Open AccessGD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas
Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system1. We have previously shown that the disialog...
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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
Immune receptor inhibition through enforced phosphatase recruitment
Antibodies that antagonize extracellular receptor–ligand interactions are used as therapeutic agents for many diseases to inhibit signalling by cell-surface receptors1. However, this approach does not directly pr...
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Article
Novel NanoLuc substrates enable bright two-population bioluminescence imaging in animals
Sensitive detection of two biological events in vivo has long been a goal in bioluminescence imaging. Antares, a fusion of the luciferase NanoLuc to the orange fluorescent protein CyOFP, has emerged as a brigh...
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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
c-Jun overexpression in CAR T cells induces exhaustion resistance
Chimeric antigen receptor (CAR) T cells mediate anti-tumour effects in a small subset of patients with cancer1–3, but dysfunction due to T cell exhaustion is an important barrier to progress4–6. To investigate th...
