# Therapeutic HPV vaccines (PVX7) for Advanced Cervical Cancer

> **NIH NIH P50** · JOHNS HOPKINS UNIVERSITY · 2024 · $252,436

## Abstract

Project Summary/Abstract
One of the major challenges for control of advanced cervical cancer is the identification, via a suitable biomarker,
of treated patients who have residual disease and are at higher risk of developing recurrence and metastasis;
and prevention of such disease recurrence and metastasis using innovative immunotherapies. The purpose of
Project 4 is two-fold: 1) to conduct a pilot study of a new therapeutic HPV vaccine to determine its safety and
tolerance in women who have completed standard-of-care therapy for cervical cancer and have no clinical
evidence of cervical cancer, but potentially still carry minimal residual disease; and 2) to test whether cell-free
HPV DNA (cfHPVDNA) in plasma provides a specific biomarker for the presence or persistence of HPV+ cancer.
Our proposed adjuvant immunotherapy targets E6 and E7 of the two genotypes that cause > 70% of cervical
cancer cases (HPV16 and HPV18). This immunotherapy comprises priming with a plasmid DNA (pBI-11) and
boosting with a recombinant vaccinia virus (TA-HPV), a combination that elicits potent CD8+ T cell responses.
The pBI-11 DNA encodes HPV16/18 E6-E7 protein linked to heat shock protein 70 (HSP70), a novel technology
that profoundly enhances antigen presentation of these otherwise poorly immunogenic antigens. Previously, we
showed that vaccination with pBI-11's predecessor, pBI-1 (which expressed only HPV16 E7 fused to HSP70),
followed by intramuscular [IM] boost with TA-HPV, was safe and triggered histologic clearance in half of HPV16+
CIN2/3 patients. We further found that boosting with TA-HPV via skin scarification [SS] generated significantly
better HPV antigen-specific CD8+ T cell-mediated immune responses. Thus, we hypothesize that after a
priming IM vaccination with pBI-11 DNA, boosting with TA-HPV vaccinia via skin scarification will elicit
a greater HPV-specific CD8+ T cell response than an IM boost, and can control minimal residual cervical
cancer remaining after standard-of-care treatment (surgery and/or chemoradiation). Ultra-sensitive
measurement of cfHPVDNA in plasma has promise as a biomarker to monitor cervical cancer disease burden,
and identify individuals at high risk for disease recurrence after primary therapy. Our preliminary data suggest
that a fully-automated, FDA-approved PCR-based test already used globally in screening can be readily adapted
to measure cfHPVDNA in plasma. To test our hypothesis, we propose: (1) To assess the safety and feasibility
of the pBI-11 DNA prime followed by TA-HPV boost (PVX7), wherein TA-HPV is administered via either IM
injection or SS, in patients with advanced cervical cancer who have completed primary therapy and have no
clinical evidence of disease; (2) To evaluate the systemic HPV16/18 E6/E7-specific cellular immune responses
to PVX7 immunotherapy regimens with TA-HPV administered via IM or SS in patients with advanced cervical
cancer who have completed primary therapy; and (3) To assess cell-free HPV16/18...

## Key facts

- **NIH application ID:** 10935442
- **Project number:** 2P50CA098252-21
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** TZYY-CHOOU WU
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $252,436
- **Award type:** 2
- **Project period:** 2003-09-30 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10935442

## Citation

> US National Institutes of Health, RePORTER application 10935442, Therapeutic HPV vaccines (PVX7) for Advanced Cervical Cancer (2P50CA098252-21). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10935442. Licensed CC0.

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