Gene-engineered T cells, represented by chimeric antigen receptor T cells (CAR-T cells), have achieved great success in hematological tumors, and gradually been applied in the clinical treatment of tumors. In 2017, two CD19-CAR products for hematological tumors were consecutively approved for marketing in America, and have shown powerful anti-tumor efficacy in non-solid tumor treatment. However, CAR-T cell therapy didn’t achieve expectant therapeutic efficacy in solid tumors due to complicated tumor microenvironment and restriction of surface tumor antigen. In addition, the cytotoxicity caused by off-target effects is more troublesome. To address these hurdles, more and more researchers have begun to explore new gene-edited T cells for solid tumor treatment, among which bispecific T cell engager T cell (BiTE T) has shown high anti-tumor efficacy in vitro evaluation and in vivo animal models and thus has attracted great attention. This review mainly discusses the current difficulties confronted by solid tumor treatment and the principles, characteristics and advantages of BiTE-T cell preparation.

Ascosphaera apis spores containing a dark-colored pigment infect honeybee larvae, resulting in a large-scale collapse of the bee colony due to chalkbrood disease. However, little is known about the pigment or whether it plays a role in bee infection caused by A. apis. In this study, the pigment was isolated by alkali extraction, acid hydrolysis, and repeated precipitation. Ultraviolet (UV) analysis revealed that the pigment had a color value of 273, a maximum absorption peak at 195 nm, and a high alkaline solubility (7.67%) and acid precipitability. Further chemical structure analysis of the pigment, including elemental composition, Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, mass spectrometry, and nuclear magnetic resonance (NMR), proved that it was a eumelanin with a typical indole structure. The molecular formula of melanin is C₁₀H₆O₄N₂, and its molecular weight is 409 Da. Melanin has hydroxyl, carboxyl, amino, and phenolic groups that can potentially chelate to metal ions. Antioxidant function analyses showed that A. apis melanin had a high scavenging activity against superoxide, hydroxyl, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, and a high reducing ability to Fe³⁺. Indirect immunofluorescence assay (IFA), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analyses showed that A. apis melanin was located on the spore wall. The spore wall localization, antioxidant activity, and metal ion chelating properties of fungal melanin have been suggested to contribute to spore pathogenicity. However, further infection experiments showed that melanin-deficient spores did not reduce the mortality of bee larvae, indicating that melanin does not increase the virulence of A. apis spores. This study is the first report on melanin produced by A. apis, providing an important background reference for further study on its role in A. apis.
Animals ; Antioxidants/pharmacology* ; Larva ; Melanins ; Molecular Structure ; Onygenales