# BCMA-targeted Oncolytic Virus for Multiple Myeloma

> **NIH NIH R43** · ANOVAC, INC. · 2020 · $222,958

## Abstract

PROJECT SUMMARY
 While the clinical outcome of multiple myeloma (MM) patients has shown remarkable improvements over
the past two decades, MM remains incurable for most patients. Thus, more efficacious therapies and novel
strategies are urgently needed. Oncolytic (cancer destroying) vaccinia virus (VV) is an appealing addition to the
current cancer therapies due to its preference for infecting and killing tumor cells and a potential for activating
the immune system component called T cells that can travel to distant sites and kill any tumor cells they find,
even those not infected by the virus. At present the activation of tumor-specific T cells is suboptimal. More
importantly, a desirable systemic intravenous administration of the oncolytic virus is not feasible due to the strong
neutralizing antibody response against it. Our goal is to engineer a VV that will efficiently stimulate the anti-
tumor immunity by directly engaging and activating resident T cells surrounding tumor cells so that they will kill
tumor cells and stop new tumors from growing. To activate T cells surrounding MM we constructed a new
molecule called a T-cell engager that couples T cells to MM and increases T-cell activation and tumor killing.
We believe that this optimized VV producing the new T-cell engager molecule will be more effective in killing
MM, compared to other oncolytic viruses. Additionally, we will modify viral glycoproteins to mask VV from
antibody recognition and neutralization, making it suitable for systemic delivery. The central hypothesis of this
study is that recombinant BCMA-TEA-VVNEV will: 1) escape neutralization by human anti-VV Abs in vitro and
in vivo; 2) direct endogenous T cells to kill BCMA+ MMs that are not infected with virus (by-stander killing),
enhancing its oncolytic activity; and 3) promote T-cell activation, resulting in the cytokines release and creation
of a pro-inflammatory microenvironment, inhibiting tumor growth. Aim 1 is to generate and test the quality of
BCMA-TEA-VVNEV in vitro. BCMA-TEA-VVNEV will be produced in our laboratory located at JLABS@TMC.
The purity and stability will be tested. In addition, the Ab neutralization, anti-tumor effect (e.g. direct and
bystander killing), replicative capacity, and T-cell activation of human BCMA-TEA-VVNEV will be tested using
transformed cell cultures and standard immune assays. Aim 2 is to evaluate the anti-tumor efficacy of BCMA-
TEA-VVNEV in vivo. BCMA-TEA-VVNEV and control VVs will be administered to tumor bearing mice and virus
replication, anti-tumor immune responses, and antitumor efficacy will be compared. Aim 3 will evaluate the
safety of BCMA-TEA-VVNEV in mouse models. BCMA-TEA-VVNEV and control VVs will be administrated to
tumor bearing mice and safety of BCMA-TEA-VVNEV will be assessed with biodistribution (tissue histology and
in vivo viral replication) and mouse survival. Our therapy is expected to have a major impact on the treatment of
MM patients with relapsed disease, wh...

## Key facts

- **NIH application ID:** 10375017
- **Project number:** 6R43CA246823-02
- **Recipient organization:** ANOVAC, INC.
- **Principal Investigator:** Xiaotong Song
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $222,958
- **Award type:** 6
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375017

## Citation

> US National Institutes of Health, RePORTER application 10375017, BCMA-targeted Oncolytic Virus for Multiple Myeloma (6R43CA246823-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10375017. Licensed CC0.

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