Advanced malignant melanoma is characterized by rapid development, poor prognosis and insensitivity to chemoradiotherapy. Immunotherapy has become one of the primary clinical treatments for malignant melanomas. In recent decades, identifying specific tumour antigens and the enhanced immunoactivity of tumour vaccines has become critical for engineering successful tumour vaccines. As a widely used vaccine carrier, heat shock protein 70 (HSP70) clearly increases the immunogenicity of tumour antigens, such as melanoma-associated antigen A1 (MAGEA1). Based on previous studies, gas-filled ultrasound microbubbles (MBs) were engineered to carry an HSP70-MAGEA1 fusion protein (FP). Following subcutaneous injection around the lymphatic nodes the FP was directly released into the lymph nodes under ultrasonic imaging. The results indicated that the microbubbles enhanced the immunoactivity of FPs more effectively than HSP70-MAGEA1 fusion alone. Additionally, HSP70-MAGEA1 delivered via microbubbles clearly inhibited and delayed the growth of MAGEA1-expressing B16 melanomas in mice and improved the survival times of these animals compared with the fusion protein alone. The results of the present study demonstrated that controlled MBs enhance the immunoactivity of FPs and also highlights novel, potential vaccine carriers and a new strategy for engineering controllable tumour vaccine designs.
Background Two-dimensional shear-wave elastography (2D-SWE) is an ultrasound elastography technique that uses shear waves to quantitatively measure tissue stiffness and it has recently been developed as a safe, real-time, and noninvasive imaging technique. The purpose of this study was to investigate the value of 2D-SWE in the diagnosis and treatment of acute compartment syndrome (ACS). Methods 2D-SWE was used to measure the elasticity values of the main muscles in the superficial compartments of the calf in 212 healthy volunteers, and the difference in the muscle elasticity values between different gender and age groups were analyzed. Nine patients with clinical suspicion of ACS were included in this study and 2D-SWE was used to measure the elasticity values of the muscles on the affected and unaffected sides, and a comparative analysis was performed. Results The mean elasticity values of the tibialis anterior (TA), peroneus longus (PL), and gastrocnemius medialis (GA) muscles in the relaxed state of the 212 healthy volunteers were 25.4 ± 3.2 kPa, 15.7 ± 1.5 kPa, and 12.1 ± 2.1 kPa, respectively. No statistically significant differences was observed in the elasticity values of the same muscle under the state of relaxation in different gender and age groups (p > 0.05). A statistically significant difference in the elasticity values of the muscle between the affected and unaffected sides in the fasciotomy group (p < 0.05, n = 5) was observed. In contrast, no difference in the elasticity values of the muscle between the affected and unaffected sides in the conservative group (p > 0.05, n = 4) was observed. There was a statistically significant difference in the elasticity values of the muscle on the affected side in the two treatment groups (p < 0.05). Conclusions When the ACS occurs, the muscle elasticity of the affected limb increases significantly. 2D-SWE is expected to be a new noninvasive technique for the assessment of ACS and may provide a potential basis for clinical diagnosis and treatment.
Retargeting the antigen-binding specificity of T cells to intracellular antigens that are degraded and presented on the tumor surface by engineering chimeric antigen receptor (CAR), also named TCR-like antibody CAR-T, remains limited. With the exception of the commercialized CD19 CAR-T for hematological malignancies and other CAR-T therapies aiming mostly at extracellular antigens achieving great success, the rareness and scarcity of TCR-like CAR-T therapies might be due to their current status and limitations. This review provides the probable optimized initiatives for improving TCR-like CAR-T reprogramming and discusses single-domain antibodies administered as an alternative to conventional scFvs and secreted by CAR-T cells, which might be of great value to the development of CAR-T immunotherapies for intracellular antigens.
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