Engineered tumor cell-derived vaccines against cancer: The art of combating poison with poison

Tumor vaccination is a promising approach for tumor immunotherapy because it presents high specificity and few side effects. However, tumor vaccines that contain only a single tumor antigen can allow immune system evasion by tumor variants. Tumor antigens are complex and heterogeneous, and identifying a single antigen that is uniformly expressed by tumor cells is challenging. Whole tumor cells can produce comprehensive antigens that trigger extensive tumor-specific immune responses. Therefore, tumor cells are an ideal source of antigens for tumor vaccines. A better understanding of tumor cell-derived vaccines and their characteristics, along with the development of new technologies for antigen delivery, can help improve vaccine design. In this review, we summarize the recent advances in tumor cell-derived vaccines in cancer immunotherapy and highlight the different types of engineered approaches, mechanisms, administration methods, and future perspectives. We discuss tumorcell-derived vaccines, including whole tumor cell components, extracellular vesicles, and cell membrane-encapsulated nanoparticles. Tumor cell-derived vaccines contain multiple tumor antigens and can induce extensive and potent tumor immune responses. However, they should be engineered to overcome limitations such as insufficient immunogenicity and weak targeting. The genetic and chemical engineering of tumor cell-derived vaccines can greatly enhance their targeting, intelligence, and functionality, thereby realizing stronger tumor immunotherapy effects. Further advances in materials science, biomedicine, and oncology can facilitate the clinical translation of tumor cell-derived vaccines

Robust Genetic Diagnosis of Split Hand-Foot Malformation by Exome Sequencing

ABSTRACT: Purpose: The present study aimed to evaluate the genetic diagnostic yield and accuracy of exome sequencing in Chinese patients with split hand–foot malformation (SHFM), a severe heterogeneous congenital anomaly characterized by hypodevelopment of the central ray of the hands and feet. Methods: A cohort of seven families and five sporadic patients with SHFM was investigated. Genomic DNA was prepared from the peripheral blood of affected as well as unaffected individuals. Whole exome sequencing (WES) was performed to identify the pathogenic mutations. Array-based comparative genomic hybridization (aCGH), CytoScan, quantitative polymerase chain reaction (qPCR), and Sanger sequencing were performed to validate the findings of WES. WES data of an additional cohort of 24 patients with non-SHFM congenital hand anomalies were analyzed as the control. Results: Pathogenic variants of TP63, c.G956A p.R319H, and c.T602A:p.L201H, were identified in two families by WES. In the remaining patients, copy number analysis of the WES data by XHMM software identified pathogenic 10q 24 duplication in five individuals from three families, which was further validated via CytoScan and qPCR; however, WES could not detect duplication in 10q24 in an additional cohort of 24 individuals with non-SHFM congenital hand anomaly. Importantly, qPCR analysis of the 10q24 region copy number revealed a definite consistency with WES data in all individuals. Genotype–phenotype analysis did not present any unique feature that could differentiate between the families with TP63 mutation and 10q24 duplication. Conclusions: Our study demonstrated that WES is an accurate and sensitive method to detect the pathogenic 10q24 duplication. Collectively, with TP63 mutation, a single WES testing could yield a diagnosis rate of about 40% (5/12) for the SHFM patients, at least in our cohort. As the genotype–phenotype correlation remains unclear, WES could be used as a cost-effective method for the genetic diagnosis of SHFM

Dendritic WS₂ nanocrystal-coated monolayer WS₂ nanosheet heterostructures for phototransistors

Two-dimensional tungsten disulfide (WS2), as one of the widely concerned members of the transition metal dichalcogenides family, has been studied broadly by its outstanding photonic and electronic properties. Since all of the research works focus on size and the number of layers, the dendritic structure WS2 has been scarcely reported. In our study, we make use of atmospheric pressure chemical vapor deposition (APCVD) to control the synthesis of dendritic WS2/monolayer WS2 heterostructures on the SiO2/Si substrate. The stacking morphology of the heterostructure is verified by AFM, Raman, and PL spectra. The effects of growth times and carrier gas flux on the quasi-epitaxial growth of WS2 films with dendritic structures have been systematically studied. In addition, the transition between fractal, dendritic, and compact morphologies with the increase of the growth times (carrier gas flux) are more significant. The compact morphology and difference of contact potential between the adjacent dendritic structures are characterized by Kelvin probe force microscopy (KPFM). Moreover, the as-fabricated FET devices exhibit excellent electronic properties (on/off ratio, carrier mobility, photoresponsivity, and response time are about 106, 11.42 cm2 V-1S1-, 46.6 mA/W, and 105.5 μs, respectively). This study paves the way for the rational design of high-sensitivity fractal-enhanced phototransistor devices for industrial and commercial applications.The authors are grateful for the financial support from the Science and Technology Service Network Initiative of the Chinese Academy of Sciences (Nos. KFJ-STS-QYZD-179 and KFJ-STS-QYZD-123), State Key Laboratory of Luminescence and Applications (NO. SKLA-2021-03), and commercial research funds (No. Y79H030)

Biomembrane and metal nanostructures for cancer theranostics: The state of the art in the combination of organic and inorganic chemistry

Nanostructures can facilitate multimodal cancer theranostics by realizing cancer-selective drug delivery. Biomembrane nanostructures (e.g., exosomes and cell membrane-derived nanostructures) are characterized by superior biocompatibility, intrinsic targeting ability and immune-modulating properties. However, their application is greatly limited by uncontrolled drug release and insufficient responsiveness, which can be overcome by metal nanostructures with distinct physicochemical properties (e.g., optoelectronic and magnetic properties). Therefore, the combination of these two nanostructures (defined as biomembrane and metal nanostructures [BMNs]) may facilitate the development of innovative nanostructures with multiple functions for cancer theranostics. BMNs have attractive advantages such as enhanced biocompatibility, natural targeting ability, intelligent responsiveness and controlled drug release, which are important for developing next-generation cancer nanostructures. This review summarizes recent advances in BMNs in cancer theranostics and highlights different types of engineering approaches and theranostic mechanisms. A series of engineering strategies for combining different biomembrane nanostructures, including liposomes, exosomes, cell membranes and bacterial membranes, with different metal nanostructures (gold, silver and copper) are summarized. The combination strategy can greatly enhance the targeting, intelligence and functionality of BMNs, thereby serving as a stronger cancer theranostic method. The challenges associated with the clinical translation of BMNs and future perspectives are also discussed