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#细胞治疗

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Oct 12Mon
  1. Mult Scler41

    Autologous haematopoietic stem cell transplantation affects paramagnetic rim lesions in multiple sclerosis.

    Autologous haematopoietic stem cell transplantation was associated with a reduction in paramagnetic rim lesions, a marker of chronic inflammation that disease-modifying therapies barely affect. In 30 transplanted people with multiple sclerosis, PRL count decreased in 40% of PRL-positive cases scanned before and after AHSCT and in 57% of those scanned after only, with no new PRL appearing. Annualised PRL disappearance rates were -0.36 and -0.43, suggesting an effect on central nervous system microglia/macrophages.

Oct 11Sun
  1. Sci Adv77

    Extracellular matrix-targeted TNC-scFv armoring enhances CAR T cell persistence and antitumor activity in solid tumors.

    Armoring CAR T cells with a secreted tenascin-C-targeted single-chain variable fragment (TNC-scFv) enhanced cytotoxicity, persistence, and reduced exhaustion in vitro and in xenograft tumor models. Single-cell transcriptomics showed the approach reprograms the tumor microenvironment toward a CD8+ T cell-enriched, functionally active immune landscape, and humanized tumor models showed robust antitumor responses with minimal systemic toxicity. Combining the armoring with interleukin-2 further increased efficacy while mitigating cytokine-associated toxicity, establishing extracellular matrix-directed armoring as a generalizable strategy for solid tumors.

    Why it matters: It offers a generalizable armoring strategy that improves CAR T cell function against solid tumors, where efficacy has been limited.

Oct 10Sat
  1. Nat Med62

    Extended follow-up of in vivo BCMA CAR-T therapy in relapsed/refractory multiple myeloma.

    Extended follow-up of in vivo BCMA CAR-T (ESO-T01), given without leukapheresis or lymphodepletion to four patients with relapsed/refractory multiple myeloma, shows no new important adverse events beyond the initial report at up to 15 months. One patient maintained stringent complete response for 15 months; median progression-free survival was 4.0 months (range 3.0-15.0). Three patients relapsed or progressed, all with extramedullary involvement, and died during follow-up, indicating limited CAR-T persistence requiring platform optimization.

Oct 6Tue
Sep 30Wed
  1. Sci Adv62

    Tumor cell-intrinsic stress states drive sensitivity to CAR T cell therapy in pancreatic cancer.

    Tumor cell-intrinsic oxidative and proteotoxic stress pathways modulate response to CAR T cell therapy in pancreatic ductal adenocarcinoma. Using in vivo CRISPR screens, single-cell genomics and immunocompetent orthotopic PDAC models, disruption of stress regulatory genes, especially Keap1 and Slc33a1, sensitized tumors to CAR T cell killing in vivo. Clinically observed Keap1 or Nfe2l2 mutations, and Keap1 loss activating the Nrf2 pathway, likewise increased susceptibility, suggesting tumor genotype could stratify patients for CAR T cell therapy.

    Why it matters: Identifies tumor stress genotype as a predictor of CAR T response, enabling patient stratification in solid tumors.

Sep 23Wed
  1. Nature Medicine64

    Persistence of mucosal CAR-T cells and inflammatory remodeling in enterocolitis associated with BCMA CAR-T cell therapy

    Enterocolitis after BCMA CAR-T cell therapy in patients with multiple myeloma is driven not only by plasma cell and B cell depletion but by expansion of cytotoxic CAR-T cells and coordinated dysregulation across intestinal compartments, a multimodal analysis shows. Mucosal CAR-T cells persist at the inflammation site. The findings support JAK inhibitors as a potential treatment for this complication.

    Why it matters: Redefines the mechanism of BCMA CAR-T enterocolitis and points to JAK inhibitors as a treatment option.

Sep 15Tue
  1. Cancer Cell65

    Depletion of an immature cord blood NK subset reverses trogocytosis-driven CAR NK dysfunction.

    An immature CD16-CD161- double-negative cord blood NK subset drives CAR NK product dysfunction: after CAR engineering these cells remained hypofunctional yet showed exaggerated trogocytosis, forming a trogocytic-antigen sink that diverted CAR engagement from tumors and caused exhaustion, fratricide and death of CD16+CD161+ double-positive effectors. Depleting the DN subset before manufacturing eliminated the antigen sink and restored antitumor activity in hematologic and solid tumor models. The work converts donor heterogeneity into an actionable manufacturing step for more potent off-the-shelf CAR NK products.

    Why it matters: It identifies a donor subset-driven mechanism of CAR NK dysfunction and a simple pre-manufacturing depletion that restores potency.

Sep 11Fri
  1. Nat Biotechnol70

    Selective RNA sequestration in biomolecular condensates directs cell fate transitions.

    P-bodies selectively sequester translationally repressed, untranslated RNAs encoding cell fate regulators in a conserved, cell type-specific manner across vertebrate developmental contexts. P-body RNA contents are controlled by microRNAs and reshaped by perturbing AGO2 or polyadenylation site usage. Manipulating P-body assembly or microRNA activity directed naive mouse and human pluripotent stem cells toward totipotency and primed human embryonic cells toward the germ cell lineage.

    Why it matters: It identifies RNA condensate manipulation as a practical method for steering pluripotent stem cell fate.

Sep 10Thu
  1. Nature67

    Efficient and precise programmable DNA knock-in without double-strand breaks.

    CRISPR kilobase-scale nickase-targeting (KNIT) editing inserts DNA fragments from 0.7 kb to over 10 kb without double-strand DNA cleavage by coupling a Cas9 nickase with a DNA donor recruiting system. It achieves up to 89% efficiency, cuts indel rates, translocations and off-target editing, restores gene expression in mutant cells, and enables non-viral CAR-T engineering with antitumour activity in vitro and in mice. This shifts kilobase-scale knock-in away from double-strand-break editing.

    Why it matters: A break-free CRISPR method reaching 89% knock-in efficiency could change how cell therapies are engineered.

Sep 8Tue
  1. Cell44

    Basement membrane turnover controls cell shape.

    Basement membrane stress relaxation time can regulate 3D cell shape, according to mathematical modeling. Molecular dynamics simulations show the stress relaxation time of a collagen IV network can be inferred from collagen IV molecule lifetime, and a new fluorescent timer reporter measures that lifetime in vivo, revealing that perlecan modifies it. The work establishes a multiscale framework linking matrix turnover to cell shape control.

Sep 7Mon
  1. Cell55

    Localized PD-1 CAR T therapy reprograms neuroinflammation.

    A single-cell RNA sequencing atlas of CSF, brain and blood from MS patients and controls identified a rare, disease-enriched subset of activated PD-1+ T follicular helper-like cells with B cell-recruiting features. PD-1-directed CAR T cells selectively depleted pathogenic PD-1+ CD4 T cells and locally released IL-10, attenuating CNS inflammation and improving clinical outcomes in murine neuroinflammation models. The work defines a CNS-localized adaptive immune circuit in MS and proposes programmable PD-1 CAR T cells to disrupt it.

    Why it matters: It nominates a CNS-localized PD-1 CAR T strategy against a newly defined immune circuit in MS.

Sep 5Sat
  1. Mol Cell55

    ER-liquid condensate contacts sequester FAM134B/C and RhoA to govern cell morphology.

    ER-phagy receptors FAM134B/C have a non-canonical role beyond ER remodeling: an amphipathic helix in FAM134B binds PRKAR1A dimers at contact sites between the ER and liquid-like PRKAR1A condensates. These contacts promote clustering of FAM134B/C with LC3B and recruit lysosomes, forming degradation hubs that sequester RhoA. In mouse pancreatic ductal adenocarcinoma cells, this cAMP-responsive pathway controls cell morphology and migration.

Sep 4Fri
  1. Nat Biotechnol61

    Integrated epigenetic and genetic programming of primary human T cells.

    An all-RNA platform using CRISPRoff and CRISPRon epigenetic editors stably turns endogenous genes off or on in primary human T cells without sustained CRISPR expression. Silencing persists through cell divisions, T cell stimulations and in vivo adoptive transfer, without the cytotoxicity or chromosomal abnormalities of multiplexed Cas9 editing. Combined Cas12a-dCas9 engineering enabled CAR knock-in plus gene silencing, improving preclinical CAR-T tumor control and survival.

Sep 2Wed
  1. Sci Immunol50

    CAR T cell-derived TNF is an early determinant of cytokine release syndrome severity.

    CAR T cell-derived TNF drives cytokine release syndrome severity by acting upstream of host inflammation. Disrupting TNF signaling in a mouse model of CRS prevented accumulation of pro-inflammatory monocyte-derived macrophages at the tumor site and blocked induction of host cytokines IL-6 and IL-1β. In humanized xenochimeras, TNF determined overall disease course including lethality.

Sep 1Tue
  1. Cell66

    Expansion and CAR engineering of granulocyte-monocyte progenitors for cellular immunotherapy.

    Defined culture conditions allow long-term ex vivo expansion of mouse and human granulocyte-monocyte progenitors (GMPs) while preserving progenitor identity, with myeloperoxidase identified as a regulator of GMP proliferation. After transfer, engineered GMPs seed hematopoietic niches, restore antibacterial defense in chronic granulomatous disease mice, and generate tumor-infiltrating macrophages. CAR-engineered GMPs suppress CD19-positive leukemia and HER2-positive solid tumors, including in immunocompetent allogeneic models using a CAR with an IgG Fc domain.

    Why it matters: It establishes expandable GMPs as a renewable platform for CAR myeloid cell therapy across liquid and solid tumors.

Aug 25Tue
  1. Nature86

    In vivo genome-wide CRISPR screens of human T cells in solid tumours.

    Genome-wide in vivo CRISPR screens of human T cells in solid tumours identify two GPCR-related targets: the P2RY8-Gα13 axis limits T cell tumour infiltration, and GNAS drives T cell dysfunction, with Gαs acting as a convergent node downstream of multiple suppressive GPCRs. GNAS knockout made T cells resistant to suppressive cues and improved efficacy in CAR and TCR models across diverse solid tumours, and combined P2RY8-GNAS knockout further enhanced tumour control.

    Why it matters: It provides an in vivo screening platform and identifies knockout targets that improve CAR and TCR T cell therapy in solid tumours.

Aug 24Mon
  1. Cell58

    The critical role of the endogenous immune compartment after CAR T cell therapy in recurrent GBM.

    Response to intracerebroventricular bivalent CAR T cell therapy in recurrent GBM was defined not by CAR T cell activation, which occurred in all patients, but by remodeling of the endogenous immune compartment in longitudinal CSF and tumor samples. Responders showed expansion of cytotoxic natural killer cells, while non-responders showed regulatory T cell expansion and abundant baseline immunosuppressive scavenger myeloid cells. The work points to combinatorial strategies that modulate host immunity to improve treatment.

    Why it matters: It shows that host immune status, not CAR T activation, determines response in recurrent GBM, guiding combination approaches.

Aug 18Tue
  1. Sci Adv58

    T cell-nanodrug conjugates synchronize vascular normalization and immune activation for solid tumor therapy.

    T cell-nanodrug conjugates link lenvatinib-loaded, PD-L1-blocking micelles to T cells via acid-labile click chemistry, synchronizing intratumoral release of lenvatinib and the PD-L1 antagonist peptide OPBP-1. The design couples vascular normalization with memory T cell differentiation, driven by PI3K-AKT-mTOR suppression and FOXO1 activation. In vivo, intratumoral CD8+ T cells and splenic memory T cells rose over sixfold in B16-OVA tumors, and a subset of MC38-OVA tumors regressed completely without systemic toxicity.

Aug 14Fri
  1. Sci Adv63

    Localized immunomodulation with cytokine-producing cells to mitigate foreign body responses in rodents and a nonhuman primate.

    Alginate-encapsulated retinal pigment epithelial cells engineered to secrete IL-10 or IL-12 prevented foreign body responses to alginate capsules in rodents, with reduced profibrotic gene expression and immune shifts consistent with macrophage and T cell regulation. Coimplanting human islets with IL-10-producing cells in diabetic C57BL/6J mice attenuated pericapsular fibrosis, preserved islet viability, and restored normoglycemia for up to 100 days, 4.76 times longer than islets alone. The approach also sustained encapsulated cell function in a healthy nonhuman primate, supporting translational feasibility and a route to less systemic immunosuppression in islet transplantation.

    Why it matters: Localized cytokine secretion from encapsulated cells extended graft function in rodents and worked in a nonhuman primate.

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