ABSTRACT
Glioblastoma (GBM) is the most common primary brain tumor, which is prone to recurrence and metastasis with poor prognosis. In recent years, immunotherapy has prolonged the survival of patients with GBM, providing a new option for the treatment of GBM. Target selection is very important for immunotherapy. Epidermal growth factor receptor variant III (EGFRvIII) is highly expressed on the surface of GBM cells in some patients, and EGFRvIII was not expressed in normal tissues. EGFRvIII are pivotal for the occurrence and progression of GBM, various targeted therapy including immunotherapy is promising to improve the efficacy of GBM. Currently, there are various approaches to target EGFRvIII, including humanized monoclonal antibodies, adoptive cell therapies and therapeutic vaccines. In this review, we focus on the preclinical and clinical findings of targeting EGFRvIII for GBM.
ABSTRACT
Objective To evaluate the feasibility and advantages of therapy of triple-negative breast cancer with Anti CD133 antibody-modified shikonin-loaded microemulsion (Anti CD133Ab-SKN-MEs). Methods Anti CD133Ab-SKN-MEs were prepared by a classic EDC/NHS conjugation technique. The drug loading efficiency and density of modified antibody were optimized using average particle size, Zeta potential and entrapment efficiency as indicators. The cell proliferation of MDA-MB-231 cells was investigated by MTT method. The cellular uptake of various formulations was qualitatively and quantitatively investigated using FITC as a probe. MDA-MB-231 cellular apoptosis induced by various treatments was evaluated by the Annexin V-PE/7-amino actinomycin D (Annexin V-PE/7-AAD) assay kit. MDA-MB-231 breast cancer stem cells (MDA-MB-231 CSC) was enriched by a suspension culture technique, and the cell morphology and proportion of CD133-positive cells were studied after treatment with various SKN formulations. The model of MDA-MB-231 tumor-bearing nude mice was established, and then injected five times every other day with saline, shikonin (SKN), SKN-MEs, and Anti CD133Ab-SKN-MEs at a dose of 4 mg/kg, to observe the tumor volume, survival time, tumor inhibition and CD133+ cells ratio during/after the treatment. Results The optimal mass ratio of SKN to total carrier was 1.0% in the preparation of Anti CD133Ab-SKN-MEs, and the optimal density of modified antibody was 0.025%.The particle was spherical with a particle size of (31.4 ± 2.1) nm, a potential of (-18.7 ± 2.5) mV and an encapsulation efficiency of (93.6 ± 2.8) %. The IC50 of Anti CD133Ab-SKN-MEs against MDA-MB-231 cells was (1.53 ± 0.43) μg/mL, the cell uptake of Anti CD133Ab-SKN-MEs was significantly higher than that of SKN-MEs and SKN, and 8 h incubation induced (67.9 ± 4.2)% cell apoptosis. Anti CD133Ab-SKN-MEs can significantly inhibit the globularity of MDA-MB-231 CSC, with a decrease in the number of CD133-positive cells. The in vivo tumor inhibition rate of Anti CD133Ab-SKN-MEs-treated mice was 78.5%, and 12.5% of tumor-bearing nude mice still survived at day 69. Moreover, the ratio of CD133-positive tumor cells within the tumor tissues was significantly reduced. Conclusion Anti CD133Ab-SKN-MEs has obvious advantages in treatment of triple-negative breast cancer, which might be related to the inhibition of tumor cells differentiation.