# Chemo-neoepitopes as novel immunotherapy for triple negative breast cancer

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $466,702

## Abstract

PROJECT SUMMARY/ABSTRACT
We propose to create a library of chemotherapy-induced cancer neoepitopes (chemo-neoepitopes) that
are shared between breast cancers, do not have to be customized for each tumor, and can be used for
immunotherapy of any cancers with mutated p53. This approach is based on the following principles:
 i. Cells experiencing DNA damage repress transcription of several cell cycle genes [1-3]
 ii. Cells with mutated p53 genes are unable to mediate this transcriptional repression in response
 to DNA damage, creating a clear transcriptional difference between normal and cancer cells
 within hosts undergoing DNA-damaging chemotherapies [1-3]
iii. Certain chemotherapies (e.g., platinums, 5 Fluorouracil, etc.), in addition to causing DNA
 damage, cause abnormal splicing leading to generation of abnormal transcripts that are recurrent
 and reproducible in cells treated with such chemotherapy [4-12]
iv. The abnormal splicing products undergo Nonsense Mediated mRNA Decay, but not before a
 Pioneer Round of translation [13-15], which is known to create antigenic epitopes [16-20].
Based on these principles and our preliminary data we posit that:
 Selected chemotherapies lead to generation of products of abnormal splicing (Chemotherapy-
 induced Products of Abnormal Splicing or CiPAS) that are not expressed in untreated cells or
 in treated cells with a functional p53, and
  CiPAS create new and predictable neoepitopes or chemo-neoepitopes, immunization with which,
 before chemotherapy will lead to tumor immunity that will contribute to tumor eradiation.
Aim 1. To identify CiPAS which are recurrently expressed during chemotherapy in breast tumors
that harbor p53 mutations. We will use bulk RNA-Seq to identify, and both bulk and single cell RT-
PCR to validate CiPAS specifically and recurrently expressed in p53-/- breast tumors.
Aim 2. To test the hypothesis that CiPAS generate cancer-specific chemo-neoepitopes that can
elicit immune protection from tumor growth:
 a. Identify chemo-neoepitopes generated from CiPAS in chemotherapy-treated mouse tumors by
 using RNA-Seq, mass-spectrometry and an integrative bioinformatics approach.
 b. Test chemo-neoepitopes for their ability to elicit CD8 and CD4 T cells and tumor rejectionusing
 the triple negative 4T1 breast cancer tumor line in syngeneic mice.
Altogether, these studies will establish the identity of mouse and human CiPAS, and will set the stage
for testing of immunogenicity and anti-tumor activity of CiPAS in cancer patients.

## Key facts

- **NIH application ID:** 10198213
- **Project number:** 1R21CA241044-01A1
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** YURIJ IONOV
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $466,702
- **Award type:** 1
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198213

## Citation

> US National Institutes of Health, RePORTER application 10198213, Chemo-neoepitopes as novel immunotherapy for triple negative breast cancer (1R21CA241044-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10198213. Licensed CC0.

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