Project 1: Optimizing a VSV Virotherapy-Based Regimen for Advanced Multiple Myeloma

Oncolytic virotherapy is a two-stage therapy. In the oncolytic phase (short-lived), the infection spreads in the tumor, killing infected cells and inflaming the microenvironment. In the immune phase (prolonged), priming and amplification of tumor-specific cytotoxic T cells (CTLs) by inflammatory mediators and phagocytosed debris from dead or dying tumor cells lead to the killing of uninfected tumor cells. VSV-IFNβ-NIS is a fast-replicating oncolytic vesicular stomatitis virus (VSV) that causes inflammatory tumor cell killing.

We previously launched an investigator-initiated first-in-human study of single-dose, single-agent intravenous VSV-IFNβ-NIS in patients with hematological malignancies that demonstrated good tolerability and encouraging signs of anti-tumor activity. Extensive correlative analyses have been conducted to characterize the kinetics of the anti-tumor immune responses and their relationship to patient-specific baseline parameters.

Now we seek to maximize the potency of intravenous VSV-IFNβ-NIS therapy through 1) repeat virus administration, 2) early suppression of the antiviral immune response, and 3) late boosting of anti-myeloma T cells by using a combination of immune suppression and immune activating regimens. The overall goal is to achieve a durable response using VSV-based virotherapy in patients with multiple myeloma.