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DDR1 has been identified as a cancer-associated receptor tyrosine kinase that is highly expressed in several malignancies relative to normal tissues. Clinically approved multi-kinase inhibitors, such as nilotinib, inhibit DDR1-mediated tumor growth in xenograft models, suggesting DDR1 might be a potential target for cancer treatments. Here, we employed an antibody-based strategy with a novel anti-DDR1 antibody-drug conjugate (ADC) for colon carcinoma treatment. We developed T4 H11 -DM4, an ADC targeting DDR1 which carries the tubulin inhibitor payload DM4. Immunohistochemical analysis of a tissue microarray containing 100 colon cancer specimens revealed that DDR1 was highly expressed in 81% of tumor tissues. Meanwhile, high expression of DDR1 was associated with poor survival in patients. In vitro, T4 H11 -DM4 exhibited potent anti-proliferative activity with half maximal inhibitory concentration (IC50 ) values in the nanomolar range in a panel of colon cancer cell lines. In vivo, the antitumor efficacy of T4 H11 -DM4 was evaluated in three colon cancer cell lines expressing different levels of DDR1. T4 H11 -DM4 achieved complete tumor regression at doses of 5 and 10 mg·kg-1 in HT-29 and HCT116 tumor models. Moreover, a correlation between in vivo efficacy of T4 H11 -DM4 and the levels of DDR1 expression on the cell surface was observed. Tumor cell proliferation was caused by the induction of mitotic arrest, indicating that the antitumor effect in vivo was mediated by DM4. In addition, T4 H11 -DM4 was efficacious in oxaliplatin-resistant colon cancer models. In exploratory safety studies, T4 H11 -DM4 exhibited no overt toxicities when multi-doses were administered at 10 mg·kg-1 into BALB/c nude mice or when a single dose up to 50 mg·kg-1 was administered into BALB/c mice. Overall, our findings highlight the potential of DDR1-targeted ADC and may facilitate the development of a new effective therapeutic strategy for colon cancer.

Ovarian cancer is considered to be the most lethal gynecologic malignancy, and despite the development of conventional therapies and new therapeutic approaches, the patient's survival time remains short because of tumor recurrence and metastasis. Therefore, effective methods to control tumor progression are urgently needed. The oncofetal tumor‐associated antigen 5T4 (trophoblast glycoprotein, TPBG) represents an appealing target for adoptive T‐cell immunotherapy as it is highly expressed on the surface of various tumor cells, has very limited expression in normal tissues, and spreads widely in malignant tumors throughout their development. In this study, we generated second‐generation human chimeric antigen receptor (CAR) T cells with redirected specificity to 5T4 (5T4 CAR‐T) and demonstrated that these CAR‐T cells can elicit lytic cytotoxicity in targeted tumor cells, in addition to the secretion of cytotoxic cytokines, including IFN‐γ, IL‐2, and GM‐CSF. Furthermore, adoptive transfer of 5T4 CAR‐T cells significantly delayed tumor formation in xenografts of peritoneal and subcutaneous animal models. These results demonstrate the potential efficacy and feasibility of 5T4 CAR‐T cell immunotherapy and provide a theoretical basis for the clinical study of future immunotherapies targeting 5T4 for ovarian cancer., We generated a second‐generation CAR‐T cell targeting 5T4 with the costimulatory molecule of 4‐1BB. 5T4 CAR‐T cells had specific cytotoxicity against ovarian cancer cells and secreted cytotoxic cytokines, including IFN‐γ, IL‐2 and GM‐CSF in vitro. 5T4 CAR‐T cells could eradicate peritoneal and subcutaneous tumor models in vivo completely in a short time without recurrence.

In this work, we proposed an effective way to fabricate a tangentially polarized composite cylindrical transducer with high electro-mechanical coupling coefficient (EMCC) by radially connecting an inner tangential polarized piezoelectric tube with an outer metal ring. The resonance frequency and EMCC of the proposed transducer are calculated according to frequency equations, which are obtained from the equivalent circuit of the transducer, and the results indicate that EMCC of the tangentially polarized cylindrical transducer is much higher than that of the cylindrical transducer polarized in radial direction. Furthermore, the Finite Element Method (FEM) model of the transducer is established and used for numerical simulation of the vibration models and the optimum configuration parameters. On the basis of those theoretical results, serials of prototype transducers are manufactured with an inner tangential polarized piezoelectric tube connecting with different outer metal cylindrical shells. The admittance characteristics of the fabricated transducers measured by Impedance Analyzer clearly demonstrate that the resonance frequencies of the transducers are in good agreement with those of simulation results, and the effective EMCC of transducers varies with the material of metal cylindrical shell, in which aluminum metal shell possesses the highest EMCC.

Aiming to effectively inspect solder joints on vehicle body-in-white, a novel detection and calibration scheme based on guided image filtering and geometrical edge selection is proposed. The scheme can be generally divided into the following three stages. In the image preprocessing stage, the homomorphic filter is utilized to adjust the illumination of the solder joint image. Then the contours of solder joints are sharpened, and the noise is eliminated by the guided image filtering. In the edge detection stage, the candidate contours are given by the improved Canny edge detection. Then, the obvious interference edges are effectively removed by the proposed geometrical edge selection method. After that, an improved K-means clustering method is used to remove the round edges of the body spots and distinguish multiple solder joints’ edges. In the calibration stage, multiple solder joints’ edges and centers are calculated by the least square method. The extensive experiments on various kinds of solder joints on vehicle body-in-white, which contained vehicle frame contours, rusted, scratched and spotted body, showed that the proposed scheme can detect and calibrate the solder joints quickly and accurately.