# Novel 'all-in-one' EV delivered RNAi treatment for NADCs within representative HIV patient models in humanized mice (Biospecimen/Cohort)

> **NIH NIH P30** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2024 · $165,613

## Abstract

Project Summary/abstract
Non-AIDS-defining cancers (NADC) are increasing in HIV-infected individuals (HIVIIs), urging the development
of novel therapeutic interventions and model systems to assess HIV’s contribution to tumor pathogenesis. Many
HIV-associated cancers result from oncogenic virus co-infections, and the high-risk human papillomavirus (HPV)
is prevalent in the development of NADCs, including head-and-neck (HNC) and anal cancers, which are
significantly elevated in HIVIIs. Importantly, the HPV viral oncogenes are involved in the transformation and
maintenance of these cancers, susceptible to targeted gene therapeutic strategies such as RNAi interference
(RNAi). However, a major hurdle preventing the development of therapeutic RNAi for HPV-associated
malignancies is delivery. Both viral and non-viral systems have been developed, but viral delivery systems are
immunogenic precluding repeat dosing, and non-viral synthetic nanoparticles are challenging to target away from
the liver with limited tumor uptake when administered systemically. We have pioneered a non-immunogenic
native extracellular vesicle system for the delivery of potent RNAi effectors to drastically advance RNAi-based
treatment for HPV-associated NADCs. However, HIVIIs have more aggressive NADCs, which are diagnosed at
a younger age with possible treatment resistance with many confounding features including chronic inflammation
and immune dysregulation, HIV viral factors that promote angiogenesis and cellular pathways associated with
treatment resistance, and possible side effects of antiretroviral therapy (ART), but representative in vivo models
are lacking to study the HIV factors affecting NADC progression and drug insensitivity. There is a need to
understand the factors affecting tumors in an HIV environment with patient-derived samples, which could be
explored through the development of immune-competent in vivo patient models that support HIV infection,
recreating a HIV-cancer ecosystem to study NADC pathogenesis. Our long-term goal is to develop innovative
interventions and models for the treatment of virally driven cancers emerging in HIVIIs, and we seek to develop
these objectives through two distinct aims: 1) characterization of an innovative EV-deliverable anti-HPV
treatment to inhibit ADC and NADCs, and 2) the assessment of the cellular profile of HPV-associated HNC
tumours from HIV+ and HIV- individuals to inform the development of representative immune-competent HIV
murine models for study factors affecting NADCs. Collectively, this work will be impactful by developing
innovative targeted treatments and representative models for HPV-associated malignancies prevalent in HIVIIs
to address the rising cases of virus-associated cancer in people living with HIV.

## Key facts

- **NIH application ID:** 11069679
- **Project number:** 3P30CA033572-41S2
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** JOHN D. CARPTEN
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $165,613
- **Award type:** 3
- **Project period:** 1997-08-01 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11069679

## Citation

> US National Institutes of Health, RePORTER application 11069679, Novel 'all-in-one' EV delivered RNAi treatment for NADCs within representative HIV patient models in humanized mice (Biospecimen/Cohort) (3P30CA033572-41S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11069679. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*