The cohesive properties and pyrolysis mechanism of an aprotic ionic liquid tetrabutylammonium bis(trifluoromethanesulfonyl)imide.

As the cohesive properties (such as the enthalpy of sublimation) of solid organic salts (or ionic liquids, ILs) are unmeasurable, a method of their indirect determination is proposed in this paper. For this purpose, the thermogravimetric analysis (TGA) and differential scanning calorimetric analysis (DSC) were carried out over a wide range of temperatures. In this study, the mathematical relationship of the thermodynamic properties between the liquid and solid phases of ILs is established using the Born-Fajans-Haber cycle, in which the sum of the vaporization enthalpy of ILs, melting enthalpy and the enthalpy of solid-solid phase transition is regarded as the sublimation enthalpy of solid organic salts. With this method, the cohesive properties of tetrabutylammonium bis(trifluoromethanesulfonyl)imide ([N4444][NTf2]), which is an aprotic IL, were successfully obtained. Additionally, the difference between the lattice energy and the cohesive energy was employed to quantitatively calculate the charge separation distance of single ion pair (r12) in the gas phase of ionic liquids for the first time, which can serve as a standard methodology to measure the closeness in distance between the anion and the cation in a gas phase ion pair. The pyrolysis mechanism of [N4444][NTf2] was also explored.

Lenalidomide enhances the efficacy of anti-BCMA CAR-T treatment in relapsed/refractory multiple myeloma: a case report and revies of the literature.

We report successful clinical experience using anti-BCMA CAR-T combined with lenalidomide in a patient who was refractory to a previous CAR-T treatment. The patient was a 51-year-old man, and was diagnosed with IgD-λ multiple myeloma(MM) in October 2015. 10 courses of chemotherapy including immunomodulators and proteasome inhibitors were used for remission and autologous hematopoietic stem cell transplantation was performed. MM relapsed after 12 months of remission. His disease continued to progress after multiple chemotherapy regimens, mouse anti-BCMA CAR-T and human-derived anti-BCMA CAR-T therapy. After a conditioning chemotherapy regimen of fludarabine and cyclophosphamide, patient took lenalidomide on day -1 and human-derived anti-BCMA CAR-T cells were infused on the next day. He suffered grade 2 cytokine-releasing syndrome(CRS) and grade 3 myelosuppression after infusion, and were resolved after symptomatic treatment. Very good partial response (VGPR) was achieved 14 days after CAR-T treatment, and had been maintained for more than 8 months. We demonstrated for the first time in patients that anti-BCMA CAR-T cell therapy combined with lenalidomide is feasible and effective in the treatment of RRMM. It provides a new strategy for RRMM patients who do not respond to anti-BCMA CAR-T cell therapy alone, and the adverse event is reversible.

CAR-T cell therapy targeting B cell maturation antigen is effective for relapsed/refractory multiple myeloma, including cases with poor performance status.

In this open-label, single-arm, phase I/II clinical trial, we evaluated the efficacy of anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell (HDS269B) therapy in 49 relapsed/refractory multiple myeloma (RRMM) patients, including 20 with Eastern Cooperative Oncology Group (ECOG) grade 3-4. After HDS269B infusion (9 × 106 CAR+ cells/kg), 17 patients (34.69%, 11 ECOG 0-2, 6 ECOG 3-4) developed cytokine release syndrome [grade 1-2: 14 patients (28.57%); grade 3: 3 patients (6.12%)]. The objective response rate (ORR) was 77%, with a complete response (CR) achieved in 47%. Ongoing response >12 months occurred in 15 patients, and was extended beyond 38 months in one patient. The median progression-free survival (PFS) and overall survival (OS) were 10 months (95% CI 5.3-14.7) and 29 months (95% CI 10.0-48.0), respectively. The PFS (12 months) and OS (18 months) rates were 41.64% and 62.76%, respectively. In patients with ECOG 0-2 and 3-4, ORR was 79.31% (23/29) and 75.0% (15/20) and PFS were 15 months (95% CI 5.4-24.6) and 4 months (95% CI 0-11.7), respectively. OS was not reached in ECOG 0-2 patients, but was 10.5 months (95% CI 0-22) in ECOG 3-4 patients. Single-cell sequencing indicated that treatment efficacy might be related to mTORC1 signaling. Thus, HDS269B therapy is safe and effective for RRMM patients, even those with ECOG 3-4.

Biological enzyme treatment of starch-based lithium-ion battery silicon-carbon composite.

Silicon/carbon composites have the disadvantages of large volume expansion and high cost, which limits their commercial application. In this study, green and economic starch was used to prepare porous starch (PS) under the action of enzymes, and then nano-silica was embedded in the PS. A PS based carbon/silicon/carbon composite was prepared by coating and carbonizing the starch slurry, which can alleviate the volume expansion of silicon. The results show that the anode composite material with 20% silicon content has a high initial capacity of 869 mAh g-1 and an initial Coulombic efficiency of 66% at 0.2 A g-1, and the specific capacity is maintained 450 mAh g-1 after 100 cycles. When the silicon content reaches 30%, the reversible capacity of the composite is 1490 mAh g-1 at a current density of 0.2 A g-1, and the capacity remains 850 mAh g-1 after 100 cycles. Its excellent properties and stability are attributed to the abundant porosity of the carbon in the starch derived layer, which improves the structural stability and electrochemical kinetics. This method provides a reference for the sustainable and environmental protection of lithium-ion battery anode materials.

In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B Cell Leukemia.

Several recent clinical trials have successfully incorporated a costimulatory domain derived from either CD28 or 4-1BB with the original CD3ζ T cell activating domain to form second-generation chimeric antigen receptors (CARs) that can increase the responsiveness and survival of CAR-engineered T (CAR-T) cells. However, a rigorous assessment of the individual benefits of these costimulatory components relative to the in vivo performance of infused T cells in patients is still lacking. Therefore, we have designed a study that allows us to investigate and compare the impact of different costimulatory signal domains on CAR-T cells in vivo. Patients with B cell leukemia were infused with a mixture of two types of CD19-specific CAR-T cells, individually bearing CD28 (28ζ) and 4-1BB (BBζ) costimulatory signaling domains. We found that such a clinical procedure was feasible and safe. Complete remission (CR) was observed in five of seven enrolled patients, with two patients exhibiting durable CR lasting more than 15 months. The in vivo expansion pattern of 28ζ and BBζ CAR-T cells varied significantly among individual patients. These results confirm a feasible method of comparing different CAR designs within individual patients, potentially offering objective insights that may facilitate the development of optimal CAR-T cell-based immunotherapies.

An alternative fully human anti-BCMA CAR-T shows response for relapsed or refractory multiple myeloma with anti-BCMA CAR-T exposures previously.

Chimeric antigen receptor T (CAR-T) cells therapy has made remarkable progress in relapsed/refractory multiple myeloma (R/R MM) treatment. Unfortunately, patients still eventually experience disease progression or relapse even after receiving anti-BCMA CAR-T therapy. At present, there are limited data on available treatment options for patients who have progressed on anti-BCMA CAR-T therapy. In this study, we evaluated the safety and efficacy of fully human anti-BCMA CAR-T (HRC0202) in seven R/R MM patients who were previously exposed to anti-BCMA CAR-T therapy. Three patients received 6.0 × 106 CAR+T cells/kg, one patient received 10.0 × 106 CAR+T cells/kg and three patients received 15.0 × 106 CAR+T cells/kg. Cytokine release syndrome (CRS) of grades 1-2 occurred in three patients (42.9%) and grade ≥3 in two patients (28.6%). Immune effector cell-associated neurotoxic syndrome (ICANS) was not observed in any of the patients. The best overall response rate (ORR) was 71.4% (5/7), with a stringent complete response/complete response (sCR/CR) achieved in three patients. The median progression-free survival (PFS) was 269 days, and median overall survival (OS) for all patients was not reached. The median peak concentration (Cmax) of HRC0202 was 30117.70 (range, 6084.35-147415.10) copies/µg DNA. This study indicated that fully human anti-BCMA CAR-T (HRC0202) is a promising treatment for R/R MM patients who relapsed or refractory from prior anti-BCMA CAR-T infusion.