# (PQ6) Mesenchymal stem cell based and immunocompetent mouse models of HIV/AIDS KSHV-driven sarcomagenesis

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $590,958

## Abstract

Kaposi’s sarcoma is an HIV/ AIDS associated malignancy that in spite of the implementation of
ART causes significant morbidity and mortality. Pathogenesis based design and testing of new
therapeutic approaches are hampered by the paucity of models that reproduce KSHV
oncogenesis in the HIV/AIDS setting. There are three major gaps to the experimental ability to
model AIDS-KS in vitro and in vivo for translational and preclinical research. 1) A continuous in
vitro KSHV-infection to tumorigenesis model that could help dissect microenvironment
contributions, and dissect viral and host contributions to viral oncogenesis 2) An in vitro and in
vivo model where HIV contributions to KSHV-sarcomagenesis can be identified and studied 3)
An immunocompetent model of KSHV-tumorigenesis that could be used to test immune-based
therapies. The Mesri and Roy Labs collaboratively developed a comprehensive set of cell and
animal models of KSHV-driven Kaposi’s sarcoma that include. I) A mesenchymal-stem cell KSHV-
infection to tumorigenesis system--a “de novo” KSHV-induced sarcomagenesis in vitro and in vivo
model, which is tightly dependent on the infected-cell microenvironment for tumorigenicity II) A
set of mouse models in which KSHV tumorigenesis occurs and can be studied in the context of
immunodeficiency, HIV-infection contributions to tumorigenesis and KSHV tumorspecific
immunosuppression III) A unique model in which KSHV-infected tumors can be transplanted and
grown in HIV infected Balb/c mice. In Aim (1) we will use the MSCs models study the role of KSHV
and HIV interactions in viral oncogenesis of HIV/AIDS-KS. In Aim (2) we will determine the
mechanisms whereby HIV infection promotes KSHV tumorigenicity in nude and
immunocompetent mice. In Aim (3), we will use our model of KSHV-tumorigenesis in HIV infected
immunocompetent mice as AIDS-KS preclinical model. We will be able to test immunological
therapies to KS such as immunomodulatory molecules, antibody-targeted therapies and
checkpoint inhibitor immunotherapies. The propose studies provide unique mouse models to
study the role of KSHV HIV co-infection in the pathogenesis of HIV/AIDS-associated Kaposi’s
sarcoma and will serve to pre-clinically evaluate novel AIDS-KS therapeutic treatments.

## Key facts

- **NIH application ID:** 10388236
- **Project number:** 5R01CA250072-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Sabita Roy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $590,958
- **Award type:** 5
- **Project period:** 2021-04-08 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388236

## Citation

> US National Institutes of Health, RePORTER application 10388236, (PQ6) Mesenchymal stem cell based and immunocompetent mouse models of HIV/AIDS KSHV-driven sarcomagenesis (5R01CA250072-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10388236. Licensed CC0.

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