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Open AccessCAR-T cell therapy targeting surface expression of TYRP1 to treat cutaneous and rare melanoma subtypes
A major limitation to develo** chimeric antigen receptor (CAR)-T cell therapies for solid tumors is identifying surface proteins highly expressed in tumors but not in normal tissues. Here, we identify Tyrosi...
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Open AccessCorrection: ERK mediates interferon gamma-induced melanoma cell death
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T cell receptor therapeutics: immunological targeting of the intracellular cancer proteome
The T cell receptor (TCR) complex is a naturally occurring antigen sensor that detects, amplifies and coordinates cellular immune responses to epitopes derived from cell surface and intracellular proteins. Thu...
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Open AccessERK mediates interferon gamma-induced melanoma cell death
Interferon-gamma (IFNγ) exerts potent growth inhibitory effects on a wide range of cancer cells through unknown signaling pathways. We pursued complementary screening approaches to characterize the growth inhi...
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Ipilimumab with or without nivolumab in PD-1 or PD-L1 blockade refractory metastatic melanoma: a randomized phase 2 trial
In this randomized phase 2 trial, blockade of cytotoxic T-lymphocyte protein 4 (CTLA-4) with continuation of programmed death protein 1 (PD-1) blockade in patients with metastatic melanoma who had received fro...
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Article
Open AccessNon-viral precision T cell receptor replacement for personalized cell therapy
T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1–3. Here we developed a clinical-grade approach based on CRISPR–Cas9 non-viral precision genome-editing to simultaneously...
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Article
Neoantigen-targeted CD8+ T cell responses with PD-1 blockade therapy
Neoantigens are peptides derived from non-synonymous mutations presented by human leukocyte antigens (HLAs), which are recognized by antitumour T cells1–14. The large HLA allele diversity and limiting clinical sa...
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Article
Multimodal single-cell and whole-genome sequencing of small, frozen clinical specimens
Single-cell genomics enables dissection of tumor heterogeneity and molecular underpinnings of drug response at an unprecedented resolution1–11. However, broad clinical application of these methods remains challen...
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Open AccessPublisher Correction: Potentiating adoptive cell therapy using synthetic IL-9 receptors
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Open AccessPotentiating adoptive cell therapy using synthetic IL-9 receptors
Synthetic receptor signalling has the potential to endow adoptively transferred T cells with new functions that overcome major barriers in the treatment of solid tumours, including the need for conditioning ch...
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Open AccessAuthor Correction: PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma
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Open AccessPD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma
Combining PD-L1 blockade with inhibition of oncogenic mitogen-activated protein kinase (MAPK) signaling may result in long-lasting responses in patients with advanced melanoma. This phase 1, open-label, dose-e...
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Article
Mutational landscape influences immunotherapy outcomes among patients with non-small-cell lung cancer with human leukocyte antigen supertype B44
Human leukocyte antigen (HLA)-B has been recognized as a major determinant of discrepancies in disease outcomes, and recent evidence indicates a role in immune checkpoint blockade (ICB) efficacy. The B44 super...
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Continuous versus intermittent BRAF and MEK inhibition in patients with BRAF-mutated melanoma: a randomized phase 2 trial
Preclinical modeling suggests that intermittent BRAF inhibitor therapy may delay acquired resistance when blocking oncogenic BRAFV600 in melanoma1,2. We conducted S1320, a randomized, open-label, phase 2 clinical...
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Combined PD-1, BRAF and MEK inhibition in advanced BRAF-mutant melanoma: safety run-in and biomarker cohorts of COMBI-i
Immune and targeted therapies achieve long-term survival in metastatic melanoma; however, new treatment strategies are needed to improve patients’ outcomes1,2. We report on the efficacy, safety and biomarker anal...
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Open AccessRaman-guided subcellular pharmaco-metabolomics for metastatic melanoma cells
Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial map** of metabolites within single cells, with the specific...
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Open AccessImpact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib ± cobimetinib: a pooled analysis of four clinical trials
We sought to identify patient subgroups with distinct postprogression overall survival (ppOS) outcomes and investigate the impact of original treatment assignment and initial postprogression treatment (ppRx) o...
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Open AccessMulti-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line
The determination of individual cell trajectories through a high-dimensional cell-state space is an outstanding challenge for understanding biological changes ranging from cellular differentiation to epigeneti...
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Publisher Correction: PAK4 inhibition improves PD-1 blockade immunotherapy
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Open AccessPersistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist
Interleukin-2 (IL-2) is a component of most protocols of adoptive cell transfer (ACT) therapy for cancer, but is limited by short exposure and high toxicities. NKTR-214 is a kinetically-engineered IL-2 recepto...
