# Accelerated Brachytherapy Forward Chemoradiation Therapy (ABC-RT) for Cervical Cancer

> **NIH NIH R37** · WASHINGTON UNIVERSITY · 2024 · $634,894

## Abstract

PROJECT SUMMARY
Survival from cervical cancer is stagnating in the United States. Despite many intervening clinical trials, the
standard of care (SOC) definitive chemoradiation therapy (CRT) has remained unchanged since the addition of
concurrent platinum-based chemotherapy to radiation in the 1990’s. Reasons for this are several-fold, and
include a patient population that is disproportionately affected by barriers to care, inherent radioresistance of
gross disease as evidenced by local recurrence after a mean primary tumor dose of >200Gy delivered with
brachytherapy plus EBRT, and insufficient systemic control, with distant failure contributing to two thirds of
cervical cancer deaths. A suboptimal immune response at the time of definitive CRT is associated with local,
regional, and distant recurrence, as well as death from cervical cancer. We have previously shown that
enrichment of immunosuppressive cells and high expression of squamous cell carcinoma antigen (SCCA),
known as SERPINB3, are associated with higher risk of recurrence after SOC CRT in cervical cancer, and that
CRT induces further infiltration of tumor permissive myeloid derived cells. Preliminary data suggest that tumor
associated macrophages, myeloid-derived suppressor cells, and regulatory T cells are increased in mid-
treatment tumor specimens from patients undergoing standard CRT. Using preclinical models, we find that
brachytherapy stimulated expression of immune-stimulatory signals to a greater degree than an equivalent dose
of EBRT. Finally, SERPINB3 directly promotes expression of chemokines that recruit immune-suppressive cells,
particularly myeloid-derived sub-populations, blunting the T-cell anti-tumor response in cervical cancer. We
hypothesize that brachytherapy alone delivered to the primary tumor prior to regional lymph node EBRT will
safely minimize patient trips, further stimulate the immune system, and potentiate the efficacy of immunotherapy.
Two aims are proposed to directly test this hypothesis: Aim 1 will determine if accelerated brachytherapy-forward
chemoradiation therapy (ABC-RT) is a safe and effective approach to shorten overall treatment time, and
maximize anti-tumor immune response through a phase I/II clinical trial for patients with locally advanced cervical
cancer. Aim 2 will determine if ABC-RT potentiates the anti-tumor activity of immune checkpoint therapies and/or
the myeloid-cell inhibitor CCR2i using a preclinical murine tumor model with a novel intracavitary brachytherapy
system developed for this proposal. Secondary endpoints to validate candidate biomarkers SERPINB3, and post
therapy FDG-PET as predictors of recurrence after this experimental approach are proposed to precisely stratify
patients for subsequent trials incorporating drug-ABC-RT combinations. Success of these aims will provide the
preliminary data to support randomized trials of ABC-RT based regimens compared to the SOC and ultimately
a paradigm shift in the definitive treatment...

## Key facts

- **NIH application ID:** 10976688
- **Project number:** 1R37CA287204-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jessika Contreras
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $634,894
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10976688

## Citation

> US National Institutes of Health, RePORTER application 10976688, Accelerated Brachytherapy Forward Chemoradiation Therapy (ABC-RT) for Cervical Cancer (1R37CA287204-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10976688. Licensed CC0.

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