Purpose This study aimed to evaluate the safety and efficacy of chimeric antigen receptor (CAR) disialoganglioside 2 (GD2)-specific (4SCAR-GD2) T cells for treatment of refractory and/or recurrent neuroblastoma (NB) in pediatric patients. Experimental design A phase I clinical study using 4SCAR-GD2 T cells for the treatment of NB in pediatric patients was conducted. This study was registered at www.clinicaltrials.gov (NCT02765243). A lentiviral CAR with the signaling domains of CD28/4-1BB/CD3ζ-iCasp9 was transduced into activated T cells. The response to 4SCAR-GD2 T-cell treatment, and 4SCAR-GD2 T-cell expansion and persistence in patients were evaluated. Toxicities were determined based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Results Twelve patients were enrolled and finally ten patients were included in this clinical trial which started from January 1, 2016, to August 1, 2017. These patients had progressive disease (PD) before CAR T-cell infusion. After 4SCAR-GD2 T-cell treatment, 6 (6/10) had stable disease (SD) at 6 months, and 4 (4/10) remained SD at 1 year and alive after 3–4 years of follow-up. Six patients died due to disease progression by the end of July 1, 2020. The median overall survival (OS) time was 25 months (95% CI, 0.00–59.43), and the median progression-free survival (PFS) time was 8 months (95% CI, 0.25–15.75). Grade 3 or 4 hematological toxicities were the common adverse events frequently occurred after fludarabine and cyclophosphamide (Flu/cy) chemotherapy. Grade 1–2 toxicities such as cytokine release syndrome (CRS) and neuropathic pain were common, but were transient and mild. Conclusions The 4SCAR-GD2 T-cell therapy demonstrated antitumor effect and manageable toxicities, indicating its potential to benefit children with refractory and/or recurrent NB.

Objective:To analyze the prognostic factors of sepsis in children with acute leukemia admitted to the pediatric intensive care unit (PICU) and to compare the efficacy of different scoring systems for predicting the outcome of children. Methods:Patients with an acute leukemia diagnosis admitted to a tertiary care university hospital PICU due to sepsis during chemotherapy between May 2015 and August 2022 were retrospectively analyzed through an electronic medical record system.Results: During this period, 693 children with acute leukemia initially diagnosed were admitted to the center, and 155 (22.3%) of them were transferred to PICU due to deterioration of the disease during treatment. Total 109 (70.3%) patients were transferred to PICU due to sepsis. Here, 17 patients was excluded (prior treatment from another hospital; referring from other hospitals; discontinued treatment; incomplete medical record). Of the 92 patients studied, the mortality rate was 35.9%. Multivariate analysis revealed that remission status, lactate level, invasive mechanical ventilation (IMV), and inotropic support within 48 hours after PICU transfer were independent risk factors for PICU mortality. The pediatric sequential organ failure assessment (PSOFA) score had the greatest predictive validity for hospital mortality (area under the receiver operating characteristic curve [AUROC]: 0.83, 95% confidence intervals [CI]: 0.74-0.92), followed by the pediatric early warning score (PEWS) (0.82, 0.73-0.91) and pediatric critical illness score (PCIS) (0.79, 0.69-0.88). Conclusion:The mortality rate among children with acute leukemia complicated with sepsis is high after being transferred to the PICU. Various scoring systems can be used to monitor the clinical status of patients, identify sepsis early, detect critical illness, and determine the optimal time for transfer to the PICU for supportive treatment, thereby improving the prognosis of these patients.

In pancreatic cancer, the activation of quiescent pancreatic stellate cells (PSCs) is a critical event that leads to a characteristic dense desmoplastic stroma. The fibrotic network resulting from the bidirectional cross talk between pancreatic cancer cells (PCCs) and PSCs creates a complex tumor microenvironment that considerably hinders drug delivery and penetration. To improve pancreatic cancer treatment, a promising parallelization strategy with cross‐action property is urgently required that can simultaneously act on PCCs and PSCs to normalize activated PSCs (aPSCs), that is reverse them back to quiescent phenotype. Herein, a novel parallelization delivery system (CoA‐A&B‐γPGA) with dual‐pathway PSC quiescence restoration functions is designed. Metformin downregulates the secretion of transforming growth factor‐beta in PCCs, and all‐trans‐retinoic acid re‐educates aPSCs. CoA‐A&B‐γPGA thus induces aPSC quiescence and homeostatic restoration of desmoplastic stroma in vitro and in vivo. Importantly, CoA‐A&B‐γPGA exhibits deep penetration, improved accumulation and long‐term retention, and enhanced combination chemotherapy effects in multicellular spheroid and xenograft models. Furthermore, this dual‐targeting and co‐delivery system shows high specificity and sensitivity for detecting pancreatic cancer in patient samples. The innovative but simple peptide amphiphile co‐assembly strategy provides a new paradigm to design desired nanomedicines for stroma‐enriched pancreatic cancer therapy.