# Anti-cancer vaccine targeting the host-parasite interface during fluke infection

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2024 · $382,600

## Abstract

Project Summary
Liver fluke infection with Opisthorchis viverrini remains problematic in East Asia and is endemic in Thailand and
Laos, where ~10 million people are infected. The public health implications of this situation are substantial since
there is no stronger link between a human malignancy and a eukaryotic pathogen than that between
cholangiocarcinoma (CCA, bile duct cancer) and infection with O. viverrini. Northeast Thailand reports the
highest incidence of CCA worldwide, with the 2014 CCA age standardized incidence rate (ASR) of 85 per
100,000, which equates to 26,000 CCA-related deaths annually. The contrast with countries without liver flukes
is stark given that incidence of CCA is less than 3 per 100,000 elsewhere (USA, 1.67 ASR, 2014).
 To survive in the biliary tract, the liver fluke actively releases excretory/secretory (ES) proteins and
extracellular vesicles (EVs) that facilitate fluke feeding and manipulation of the host immune response, and
ultimately modify cellular homeostasis that contributes to malignant transformation. Our hypothesis is that
targeting proteins that are essential for several discrete facets of parasitism and/or are known carcinogens via a
multi-valent vaccine will deliver a novel anti-infection/ anti-cancer therapy. We will address this hypothesis
through the following aims: Aim 1. Explore the importance of key fluke ES proteins in host-parasite
communication and leverage the findings to prioritize their selection as vaccine antigens. Aim 2. Determine
whether mRNA and/or protein subunit vaccines induce antibodies that reduce both fluke burdens and CCA
incidence in the hamster infection-cancer model. This proposal targets liver fluke ES proteins which drive the
phenotypic hallmarks of cancer in the biliary epithelium: 1) the granulin-like growth factor, Ov-GRN-1, known to
induce rampant cholangiocyte proliferation; 2) the tetraspanin, Ov-TSP-2, a key element of EVs and host-cell
communication; 3) the Ov-catF cysteine protease, a key component of the protein digestion cascade; and 4) the
Ov-M60mucinase which degrades host defensive mucus in the bile ducts.
 The conceptual innovation we utilize is a rodent model of human carcinogenesis where liver fluke
infection is a known risk factor. Technical innovations include gene knockout in the liver fluke, targeting key
pathogenic and nutritional processes, and combining the findings to develop vaccination against fluke infection
and the infection-induced cancer. These studies will determine whether fluke proteins that communicate at the
host-parasite interface represent the Achilles’ heel of this carcinogenic parasite. Targeting fluke-host
communication in combination with nutrient acquisition pathways may ultimately combat liver fluke-induced bile
duct cancer in the form of an anti-fluke, and indeed anti-cancer vaccine, a public health development with the
potential to benefit millions of (often impoverished) residents of endemic regions in East Asia.

## Key facts

- **NIH application ID:** 10981302
- **Project number:** 2R01CA164719-11A1
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Paul J Brindley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $382,600
- **Award type:** 2
- **Project period:** 2012-09-21 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981302

## Citation

> US National Institutes of Health, RePORTER application 10981302, Anti-cancer vaccine targeting the host-parasite interface during fluke infection (2R01CA164719-11A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10981302. Licensed CC0.

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