Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial.

Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B.

Constitutive Interferon Pathway Activation in Tumors as an Efficacy Determinant Following Oncolytic Virotherapy.

Background: Attenuated measles virus (MV) strains are promising agents currently being tested against solid tumors or hematologic malignancies in ongoing phase I and II clinical trials; factors determining oncolytic virotherapy success remain poorly understood, however.

Methods: We performed RNA sequencing and gene set enrichment analysis to identify pathways differentially activated in MV-resistant (n = 3) and -permissive (n = 2) tumors derived from resected human glioblastoma (GBM) specimens and propagated as xenografts (PDX). Using a unique gene signature we identified, we generated a diagonal linear discriminant analysis (DLDA) classification algorithm to predict MV responders and nonresponders, which was validated in additional randomly selected GBM and ovarian cancer PDX and 10 GBM patients treated with MV in a phase I trial.

Inhibition of the Aurora A kinase augments the anti-tumor efficacy of oncolytic measles virotherapy.

Oncolytic measles virus (MV) strains have demonstrated broad spectrum preclinical anti-tumor efficacy, including breast cancer. Aurora A kinase controls mitotic spindle formation and has a critical role in malignant transformation. We hypothesized that the Aurora A kinase inhibitor MLN8237 (alisertib) can increase MV oncolytic effect and efficacy by causing mitotic arrest.

Restoration of epigenetically silenced SULF1 expression by 5-aza-2-deoxycytidine sensitizes hepatocellular carcinoma cells to chemotherapy-induced apoptosis.

Background: Hepatocellular carcinoma (HCC) is the second most frequent cause of cancer death worldwide. Sulfatase 1 (SULF1) functions as a tumor suppressor in HCC cell lines , but also has an oncogenic effect in some HCCs .

Aim: To examine the mechanisms regulating SULF1 and its function in HCC.

Oncolytic measles virus expressing the sodium iodide symporter to treat drug-resistant ovarian cancer.

Edmonston vaccine strains of measles virus (MV) have significant antitumor activity in mouse xenograft models of ovarian cancer. MV engineered to express the sodium iodide symporter gene (MV-NIS) facilitates localization of viral gene expression and offers a tool for tumor radiovirotherapy. Here, we report results from a clinical evaluation of MV-NIS in patients with taxol- and platinum-resistant ovarian cancer.