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This document is a correction notice for an article titled "Targeted Extracellular Vesicles Delivered Verrucarin A to Treat Glioblastoma" published in the journal Biomedicines. The correction states that there was an error in Figure 6 of the original publication, and a corrected version of the figure is provided. The authors assure that the scientific conclusions of the article are unaffected by this error. The correction was approved by the Academic Editor, and the original publication has been updated accordingly. The article includes a graph showing the in vivo evaluation of the anti-GBM efficacy of mAb-EV-Ver-A, as well as representative images and H&E staining of brain tissue sections. The authors of the article are Kai Chen, Yingnan Si, Jia-Shiung Guan, Zhuoxin Zhou, Seulhee Kim, Taehyun Kim, Liang Shan, Christopher D. Willey, Lufang Zhou, and Xiaoguang Liu. [Extracted from the article]

Triple‐negative breast cancers (TNBCs) are highly aggressive, metastatic and recurrent. Cytotoxic chemotherapies with limited clinical benefits and severe side effects are the standard therapeutic strategies, but, to date, there is no efficacious targeted therapy. Literature and our data showed that epidermal growth factor receptor (EGFR) is overexpressed on TNBC cell surface and is a promising oncological target. The objective of this study was to develop an antibody‐drug conjugate (ADC) to target EGFR+ TNBC and deliver high‐potency drug. First, we constructed an ADC by conjugating anti‐EGFR monoclonal antibody with mertansine which inhibits microtubule assembly via linker Sulfo‐SMCC. Second, we confirmed the TNBC‐targeting specificity of anti‐EGFR ADC by evaluating its surface binding and internalization in MDA‐MB‐468 cells and targeting to TNBC xenograft in subcutaneous mouse mode. The live‐cell and live‐animal imaging with confocal laser scanning microscopy and In Vivo Imaging System (IVIS) confirmed the TNBC‐targeting. Finally, both in vitro toxicity assay and in vivo anti‐cancer efficacy study in TNBC xenograft models showed that the constructed ADC significantly inhibited TNBC growth, and the pharmacokinetics study indicated its high circulation stability. This study indicated that the anti‐EGFR ADC has a great potential to against TNBC. [ABSTRACT FROM AUTHOR]

Mitochondria are important in various aspects of cancer development and progression. Targeting mitochondria in cancer cells holds great therapeutic promise, yet current strategies to specifically and effectively destroy cancer mitochondria in vivo are limited. Here, we developed mitochondrial luminoptogenetics (mLumiOpto), an innovative mitochondrial-targeted luminoptogenetics gene therapy designed to directly disrupt the inner mitochondrial membrane potential and induce cancer cell death. The therapeutic approach included synthesis of a blue light-gated cationic channelrhodopsin in the inner mitochondrial membrane and coexpression of a blue bioluminescence-emitting nanoluciferase in the cytosol of the same cells. The mLumiOpto genes were selectively delivered to cancer cells in vivo by an adeno-associated virus carrying a cancer-specific promoter or cancer-targeted mAB-tagged exosome-associated adeno-associated virus. Induction with nanoluciferase luciferin elicited robust endogenous bioluminescence, which activated cationic channelrhodopsin, triggering cancer cell mitochondrial depolarization and subsequent cell death. Importantly, mLumiOpto demonstrated remarkable efficacy in reducing tumor burden and killing tumor cells in glioblastoma and triple-negative breast cancer xenograft mouse models. Furthermore, the approach induced an antitumor immune response, increasing infiltration of dendritic cells and CD8+ T cells in the tumor microenvironment. These findings establish mLumiOpto as a promising therapeutic strategy by targeting cancer cell mitochondria in vivo. Significance: mLumiOpto is a next generation optogenetic approach that employs selective delivery of genes to cancer cells to trigger mitochondrial depolarization, effectively inducing cell death and reducing tumor burden., (©2024 The Authors; Published by the American Association for Cancer Research.)

Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous disease that often relapses following treatment with standard radiotherapies and cytotoxic chemotherapies. Combination therapies have potential for treating refractory metastatic TNBC. In this study, we aimed to develop an antibody-drug conjugate with dual payloads (DualADC) as a chemoimmunotherapy for TNBC. The overexpression of an immune checkpoint transmembrane CD276 (also known as B7-H3) was associated with angiogenesis, metastasis, and immune tolerance in more than 60% of patients with TNBC. Development of a mAb capable of targeting the extracellular domain of surface CD276 enabled delivery of payloads to tumors, and a platform was established for concurrent conjugation of a traditional cytotoxic payload and an immunoregulating Toll-like receptor 7/8 agonist to the CD276 mAb. The DualADC effectively killed multiple TNBC subtypes, significantly enhanced immune functions in the tumor microenvironment, and reduced tumor burden by up to 90% to 100% in animal studies. Single-cell RNA sequencing, multiplex cytokine analysis, and histology elucidated the impact of treatment on tumor cells and the immune landscape. This study suggests that the developed DualADC could represent a promising targeted chemoimmunotherapy for TNBC. Significance: An anti-CD276 monoclonal antibody conjugated with both a cytotoxic drug and an immune boosting reagent effectively targets triple-negative breast cancer by inducing tumor cell death and stimulating immune cell infiltration., (©2024 The Authors; Published by the American Association for Cancer Research.)

Adeno-associated viruses (AAVs) have been well characterized and used to deliver therapeutic genes for diseases treatment in clinics and basic research. This study used the triple transient transfection of AAV-DJ/8 as a model expression system to develop and optimize the laboratory production of AAV for research and pre-clinical applications. Specifically, various production parameters, including host cell, transfection reagent, cell density, ratio of plasmid DNA and cells, gene size, and production mode, were tested to determine the optimal process. Our results showed that the adherent production using HEK 293AAV with calcium transfection generated the highest volumetric productivity of 7.86x10 9 gc/mL. The optimal suspensive production using HEK 293F had best AAV productivity of 5.78x10 9 gc/mL in serum-free medium under transfection conditions of transfection density of 0.4x10 6 cells/mL, plasmid DNA:cells ratio of 1.6 μg:10 6 cells and synthesized cationic liposomes as transfection reagent. The similar AAV productivity was confirmed at scales of 30 mL - 450 mL in shaker and/or spinner flasks. The in vitro transfection and in vivo infection efficiency of the harvested AAV-DJ/8 carrying luciferase reporter gene was confirmed using cell line and xenograft mouse model, respectively. The minimal or low purification recovery rate of AAV-DJ/8 in ion-exchange chromatography column and affinity column was observed in this study. In summary, we developed and optimized a scalable suspensive production of AAV to support the large-scale preclinical animal studies in research laboratories., Competing Interests: Conflicts of Interest The authors declare no conflict of interest.