To realize the potential of MSCs, bioengineering is needed to boost potency and control heterogeneity.

With the increased worldwide burden of cancer, including aggressive and resistant cancers, oncolytic virotherapy has emerged as a viable therapeutic option. Oncolytic herpes simplex virus (oHSV) can be genetically engineered to target cancer cells while sparing normal cells. This leads to the direct killing of cancer cells and the activation of the host immunity to recognize and attack the tumor. Different variants of oHSV have been developed to optimize its antitumor effects. In this review, we discuss the development of oHSV, its antitumor mechanism of action and the clinical trials that have employed oHSV variants to treat different types of tumor.

CRISPR-engineered receptor-specific self-targeted tumor cells demonstrate antitumor efficacy in vitro and in vivo.

Proteins are densely packed in cells and tissues, where they form complex nanostructures. Expansion microscopy (ExM) variants have been used to separate proteins from each other in preserved biospecimens, improving antibody access to epitopes. Here, we present an ExM variant, decrowding expansion pathology (dExPath), that can expand proteins away from each other in human brain pathology specimens, including formalin-fixed paraffin-embedded (FFPE) clinical specimens. Immunostaining of dExPath-expanded specimens reveals, with nanoscale precision, previously unobserved cellular structures, as well as more continuous patterns of staining. This enhanced molecular staining results in observation of previously invisible disease marker–positive cell populations in human glioma specimens, with potential implications for tumor aggressiveness. dExPath results in improved fluorescence signals even as it eliminates lipofuscin-associated autofluorescence. Thus, this form of expansion-mediated protein decrowding may, through improved epitope access for antibodies, render immunohistochemistry more powerful in clinical science and, perhaps, diagnosis.

Cellular therapies offer a promising therapeutic strategy for the highly malignant brain tumor, glioblastoma (GBM). However, their clinical translation is limited by the lack of effective target identification and stringent testing in pre-clinical models that replicate standard treatment in GBM patients. In this study, we show the detection of cell surface death receptor (DR) target on CD146-enriched circulating tumor cells (CTC) captured from the blood of mice bearing GBM and patients diagnosed with GBM. Next, we developed allogeneic “off-the-shelf” clinical-grade bifunctional mesenchymal stem cells (MSC^Bif) expressing DR-targeted ligand and a safety kill switch. We show that biodegradable hydrogel encapsulated MSC^Bif (EnMSC^Bif) has a profound therapeutic efficacy in mice bearing patient-derived invasive, primary and recurrent GBM tumors following surgical resection. Activation of the kill switch enhances the efficacy of MSC^Bif and results in their elimination post-tumor treatment which can be tracked by positron emission tomography (PET) imaging. This study establishes a foundation towards a clinical trial of EnMSC^Bif in primary and recurrent GBM patients.

MicroRNA (miR) are a class of small non-coding RNA that are involved in post-transcriptional gene regulation. Altered expression of miR has been associated with several pathological conditions. MicroRNA-124 (miR-124) is an abundantly expressed miR in the brain as well as the thymus, lymph nodes, bone marrow, and peripheral blood mono-nuclear cells. It plays a key role in the regulation of the host immune system. Emerging studies show that dysregulated expression of miR-124 is a hallmark in several cancer types and it has been attributed to the progression of these malignancies. In this review, we present a comprehensive summary of the role of miR-124 as a promising therapeutic gateway in oncology.