A strategy of creating stretchable conducting hydrogels for emerging soft electronics is reported. With ice-templated low-temperature polymerization (ITLP), the conducting gel exhibited a hierarchical dendritic microstructure with mitigated nanoaggregation and significantly enhanced electrical conductivity and toughness. Using such gels, strain sensors presented a broad sensing range and high sensitivity for health monitoring. Stretchable solid-state supercapacitors demonstrated remarkable capacitance and flexibility as wearable energy-storage devices. Such a general ITLP method may create diverse soft-electronic materials for energy, healthcare, and robotic applications.

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Implantable bioelectronics represent an emerging technology that can be integrated into the human body for diagnostic and therapeutic functions. Power supply devices are an essential component of bioelectronics to ensure their robust performance. However, conventional power sources are usually bulky, rigid, and potentially contain hazardous constituent materials. The fact that biological organisms are soft, curvilinear, and have limited accommodation space poses new challenges for power supply systems to minimize the interface mismatch and still offer sufficient power to meet clinical‐grade applications. Here, recent advances in state‐of‐the‐art nonconventional power options for implantable electronics, specifically, miniaturized, flexible, or biodegradable power systems are reviewed. Material strategies and architectural design of a broad array of power devices are discussed, including energy storage systems (batteries and supercapacitors), power devices which harvest sources from the human body (biofuel cells, devices utilizing biopotentials, piezoelectric harvesters, triboelectric devices, and thermoelectric devices), and energy transfer devices which utilize sources in the surrounding environment (ultrasonic energy harvesters, inductive coupling/radiofrequency energy harvesters, and photovoltaic devices). Finally, future challenges and perspectives are given.

Oriented microstructures are widely found in various biological systems for multiple functions. Such anisotropic structures provide low tortuosity and sufficient surface area, desirable for the design of high‐performance energy storage devices. Despite significant efforts to develop supercapacitors with aligned morphology, challenges remain due to the predefined pore sizes, limited mechanical flexibility, and low mass loading. Herein, a wood‐inspired flexible all‐solid‐state hydrogel supercapacitor is demonstrated by morphologically tuning the aligned hydrogel matrix toward high electrode‐materials loading and high areal capacitance. The highly aligned matrix exhibits broad morphological tunability (47–12 µm), mechanical flexibility (0°–180° bending), and uniform polypyrrole loading up to 7 mm thick matrix. After being assembled into a solid‐state supercapacitor, the areal capacitance reaches 831 mF cm−2 for the 12 µm matrix, which is 259% times of the 47 µm matrix and 403% times of nonaligned matrix. The supercapacitor also exhibits a high energy density of 73.8 µWh cm−2, power density of 4960 µW cm−2, capacitance retention of 86.5% after 1000 cycles, and bending stability of 95% after 5000 cycles. The principle to structurally design the oriented matrices for high electrode material loading opens up the possibility for advanced energy storage applications.

Purpose: Since CD7 may represent a potent target for T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) immunotherapy, this study aimed to investigate safety and efficacy of autologous CD7-chimeric antigen receptor (CAR) T cells in relapsed and refractory (R/R) T-ALL/LBL patients, as well as its manufacturing feasibility. Experimental Design: Preclinical phase was conducted in NPG{trade mark, serif} mice injected with Luc+ GFP+CCRF-CEM cells. Open label phase I clinical trial (NCT04004637) enrolled patients with R/R CD7-positive T-ALL/LBL who received autologous CD7-CAR T cells infusion. Primary endpoint was safety, secondary endpoints included efficacy, pharmacokinetic and pharmacodynamic parameters. Results: CD7 blockade strategy was developed using tandem CD7 nanobody VHH6 coupled with an ER/Golgi-retention motif peptide to intracellularly fasten CD7 molecules. In preclinical phase CD7 blockade CAR T-cells prevented fratricide and exerted potent cytolytic activity, significantly relieving leukemia progression and prolonged the median survival of mice. In clinical phase, the complete remission (CR) rate was 87.5% (7/8) three months after CAR T cells infusion; one leukemia patient achieved minimal residual disease negative CR and one lymphoma patient achieved CR for more than 12 months. Majority of patients (87.5%) only had grade 1 or 2 cytokine release syndrome with no T-cell hypoplasia or any neurological toxicities observed. The median maximum concentration of CAR T cells was 857.2 cells/µL at approximately 12 days and remained detectable up to 270 days. Conclusions: Autologous nanobody-derived fratricide-resistant CD7-CAR T cells demonstrated a promising and durable antitumor response in R/R T-ALL/LBL with tolerable toxicity, warranting further studies in highly aggressive CD7-positive malignancies.

Natural killer (NK) cells play a pivotal role in monoclonal antibody-mediated immunotherapy through the antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. NK-92MI is an interleukin-2 (IL-2)-independent cell line, which was derived from NK-92 cells with superior cytotoxicity toward a wide range of tumor cells in vitro and in vivo. Nonetheless, the Fc-receptor (CD16) that usually mediates ADCC is absent in NK-92 and NK-92MI cells. To apply NK-92MI cell-based immunotherapy to cancer treatment, we designed and generated two chimeric receptors in NK-92MI cells that can bind the Fc portion of human immunoglobulins. The construct includes the low-affinity Fc receptor CD16 (158F) or the high-affinity Fc receptor CD64, with the addition of the CD8a extracellular domain, CD28 transmembrane domains, two costimulatory domains (CD28 and 4-1BB), and the signaling domain from CD3ζ. The resulting chimeric receptors, termed CD16-BB-ζ and CD64-BB-ζ, were used to generate modified NK-92MI cells expressing the chimeric receptor, which were named NK-92MIhCD16 and NK-92MIhCD64 cells, respectively. We found that NK-92MIhCD16 and NK-92MIhCD64 cells significantly improved cytotoxicity against CD20-positive non-Hodgkin's lymphoma cells in the presence of rituximab. These results suggest that the chimeric receptor-expressing NK-92MI cells may enhance the clinical responses to currently available anticancer monoclonal antibodies.

3026 Background: CD7 represents a potential target for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL). We developed CD7 nanobody derived chimeric antigen receptor T-cells (CD7-CART), and established a non-gene editing strategy by anchoring CD7 in the ER and/or Golgi to overcome the CART fratricide. Methods: This single-arm, open-label, phase I study is to investigate CD7-CART cell manufacturing feasibility without contamination of malignant T cells, and the safety and efficacy of the CART on patients with CD7 positive relapsed/refractory T-ALL/T-LBL. 3 subjects, identified as both CD4 and CD8 negative T-ALL or T-LBL were enrolled. CART cells were manufactured by using CD4+/CD8+ sorted T cells from leukapheresis. All patients (Pts) were pretreated with Flu/Cy prior to CART infusion. 1x106/kg CART cells were given to case 2 and 3, while 1.5x106/kg to case 1. Results: Case 1 was diagnosed as refractory ALL with myeloid differentiation, who had received intensive chemotherapy and allogeneic hematopoietic stem cell microtransplantation. Case 2 was diagnosed as ALL (T/B mixed type) but relapsed with CNS involvement, and received radiotherapy in addition to intensive chemotherapy. Prior to CART infusion, case 2 had no abnormal B cells but 17.69% of abnormal early T cellsfrom BM. Case 3 had stage VI of T-LBL, which recurred after multi-cycle chemotherapy of BFM-90 regimen and autologous SCT. After CART treatment, no neurotoxicity was observed in all pts. Case 1 had grade 3 CRSwhile case 2 and 3 had grade 1, although increased IL-6 was detected in all pts. Significant CART expansion and persistence were observed in case 2 and 3, and MRD negative CR was confirmed on day 28 in both pts. The number of generalized lymphadenopathy, lymph node size, and the degree of metabolism were all significantly reduced in case 3. Case 1 had only moderate CART expansion, but abnormal early T cells from BM decreased from 70.03% to 19.57% on day 30. After CART infusion, the number of peripheral abnormal T cells became either undetectable in case 2 and 3, or significantly decreased in case 1. Interestingly, CART had unsustained effect on normal T cells in all pts. As of Feb-10-2020, case 1 has 5 months of OS, including 3 months of PFS. Case 2 and 3 has reached 2 and 1 months of PFS and is still in remission. Conclusions: CD7-CART cells can be manufactured without contamination of malignant T cells. CD7-CART therapy is well-tolerated and has great therapeutic potential for relapsed/refractory CD7 positive T cell malignancies. Clinical trial information: NCT04004637 .

Recent progress in the adhesion mechanism of mussels has led to great excitement in the field of adhesive materials. Although great progress has been made in the mussel adhesion mechanism and underwater adhesives, there are still many unknowns and challenges in this area. Thus, it is highly important to review the recent progress in mechanisms of mussel adhesion and mussel-inspired adhesives and predict trends for the future. In this review, we (1) summarize the research progress in fundamental interaction mechanisms in natural mussels; (2) discuss the application of the mussel interaction mechanism in the biomimetic mussel adhesive materials, from permanent/high-strength adhesives to temporary/smart adhesives; (3) briefly state the potential applications of the mussel-inspired adhesives in multiple fields, such as engineering applications, smart robotics and biomedicine; (4) summarize the future perspectives and unsolved challenges of mussel adhesion mechanisms and mussel-inspired adhesive materials. We envision that this review will provide an insightful perspective in understanding the mussel adhesion mechanism and directions to further explore, and promote the development of novel biomimetic mussel adhesive materials.