Background Endogenous or iatrogenic antitumor immune responses can improve the course of follicular lymphoma (FL), but may be diminished by immune checkpoints in the tumor microenvironment. These may include effects of programmed death (PD)-1, a co-inhibitory receptor that impairs T-cell function and is highly expressed on intratumoral T cells. In a Phase II trial, we determined the activity of pidilizumab, a humanized anti-PD-1 monoclonal antibody, with rituximab in patients with relapsed FL. Methods FL patients with rituximab-sensitive disease relapsing after 1–4 prior therapies were eligible. Pidilizumab was administered at 3 mg/kg every 4 weeks for 4 infusions, plus 8 optional infusions every 4 weeks for patients with stable disease or better. Starting 2 weeks after the first infusion of pidilizumab, rituximab was given at 375 mg/m2 weekly for 4 weeks. The primary endpoint was to assess the overall response rate. Analysis was by intention to treat. Peripheral blood and tumor biopsies were studied to assess immunological effects of pidilizumab. This trial has been completed and was registered at www.clinicaltrials.gov as NCT00904722. Findings The combination was well-tolerated, with no autoimmune or therapy-related grade 3/4 toxicities. The most common grade 1 adverse events were anemia (14 patients) and fatigue (13 patients), and the most common grade 2 adverse event was respiratory infection (5 patients). Overall 19/29 (66%) and complete 15/29 (52%) response rates in 29 evaluable patients were high, with tumor regression in 25/29 (86%) of patients. Median progression-free survival was 18.8 months (95% CI: 14.7 months to not reached). The median response duration for the 19 responders was 20.2 months (95% CI: 13.9 months to not reached). Correlative studies of blood and tumor provided insights into predicting response and understanding mechanisms involved. Interpretation Pidilizumab with rituximab is well-tolerated and its activity compared favorably to historical retreatment with rituximab monotherapy in patients with relapsed FL. Our results establish that immune checkpoint blockade is worthy of further study in FL. Funding National Institutes of Health, Leukemia and Lymphoma Society, Cure Tech Ltd, and UT MD Anderson Cancer Center.

Elucidating the coordination structures and assembling modes of atomically precise metal nanoclusters (NCs) remains a hot topic as it gives answers to underlying mechanism of nanomaterials and bulk materials in...

Generally, patients with pancreatic ductal adenocarcinoma, especially those with wide metastatic lesions, have a poor prognosis. Recently, a breakthrough in improving their survival has been achieved by using first-line chemotherapy, such as gemcitabine plus nab-paclitaxel or oxaliplatin plus irinotecan plus 5-fluorouracil plus calcium folinate. Unfortunately, regimens with high effectiveness are still absent in second- or later-line settings. In addition, although immunotherapy using checkpoint inhibitors definitively represents a novel method for metastatic cancers, monotherapy using checkpoint inhibitors is almost completely ineffective for pancreatic ductal adenocarcinomas largely due to the suppressive immune milieu in such tumors. Critically, the genomic alteration pattern is believed to impact cancer immune environment. Surprisingly, KRAS gene mutation is found in almost all pancreatic ductal adenocarcinomas. Moreover, KRAS mutation is indispensable for pancreatic carcinogenesis. On these bases, a relationship likely exists between this oncogene and immunosuppression in this cancer. During pancreatic carcinogenesis, KRAS mutation-driven events, such as metabolic reprogramming, cell autophagy, and persistent activation of the yes-associated protein pathway, converge to cause immune evasion. However, intriguingly, KRAS mutation can dictate a different immune environment in other types of adenocarcinoma, such as colorectal adenocarcinoma and lung adenocarcinoma. Overall, the KRAS mutation can drive an immunosuppression in pancreatic ductal adenocarcinomas or in colorectal carcinomas, but this mechanism is not true in KRAS-mutant lung adenocarcinomas, especially in the presence of TP53 inactivation. As a result, the response of these adenocarcinomas to checkpoint inhibitors will vary.

Co-crystallization is an important aspect of crystal engineering that has found major applications in the development and manufacture of pharmaceutical drugs but is rarely invoked in the development of magnetic materials. Co-crystals have been serendipitously obtained instead of the usual coordination polymers from the organic radical, 2,2-pentamethylene-4,4,5,5tetramethylimidazolidine-l-oxyl, and coordination complexes, cis-M II (hfac) 2 (H 2 O) 2 , where M = Co or Mn and hfac = hexafluoroacetylacetonato. The extensive intramolecular H-bond is the cause for the segregation of the two entities but the supramolecular interactions between these two neutral building blocks resulted in a rare chiral co-crystal system. The directional properties of the supramolecular interactions,and F•••CH 2 , have been identified as working in tandem to generate the chirality from achiral components in achiral solvents. The absence of charge or proton transfer as suggested by X-ray structural analyses (bond lengths and angles), values of the magnetic moments, and lack of magnetic exchange between the metal spin and that of the organic radical are characteristics to define these two solids as genuine co-crystals. We therefore proposed that these solids be more effective as biomarkers than the pure radical. A comparison of their properties to related radicals is provided.

Six series of quinazoline derivatives bearing oxazole or imidazole (8a–f, 9a–f, 10a–d, 11a–f, 12a–d and 13a–i) were designed, synthesized and their IC50 values evaluated against three cancer cell lines (A549, MCF-7 and PC-3).

A novel alkynyl-stabilized silver-copper alloy nanocluster with the composition of [Ag13-xCu6+x(tBuC6H4C≡C)14(PPh3)6](SbF6)3 was prepared by (PPh3)2CuBH4-mediated reduction approach. The nanocluster featured a centred disordered-octahedral Ag7Cu6 kernel, which was protected by hybrid...

Objective To review the pharmacological characteristics, clinical evidence, and place in therapy of satralizumab for the treatment of neuromyelitis optica spectrum disorders (NMOSDs). Data Sources A comprehensive literature search was conducted in PubMed (January 2000 to October 15, 2020). Key search terms included satralizumab and neuromyelitis optica spectrum disorders. Other sources were derived from product labeling and ClinicalTrials.gov. Study Selection and Data Extraction All English-language articles identified from the data sources were reviewed and evaluated. Phase I, II, and III clinical trials were included. Data Synthesis NMOSD is an autoimmune disease characterized by inflammatory lesions in the optic nerves and spinal cord. Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor. Phase III trials showed that protocol-defined relapse was 30% for satralizumab and 50% for placebo ( P = 0.018) when patients with NMOSD were treated with satralizumab monotherapy; protocol-defined relapse was 20% for satralizumab and 43% for placebo ( P = 0.02) when satralizumab was added to immunosuppressant treatment. Satralizumab is generally well tolerated, with common adverse effects including injection-related reaction. Relevance to Patient Care and Clinical Practice Satralizumab has the potential to become a valuable treatment option for patients with NMOSD. Conclusion Satralizumab appears to be safe and effective as monotherapy or in combination with an immunosuppressant for patients with NMOSD and has the potential to become a valuable treatment option for these patients.

The spontaneous synthesis of nitrogen and phosphorus co-doped carbon dots was reported, and they were used as a probe for chloramphenicol.