# IRP-3

> **NIH NIH P50** · ROSWELL PARK CANCER INSTITUTE CORP · 2022 · $323,091

## Abstract

ABSTRACT: Despite increasing efficacy for standard of care of ovarian cancer (OvCa), the overall five-year
survival of OvCa patients is only 47.6%. Polyclonal T cell responses against multiple cancer- and patient-
specific antigens are the key element of effective cancer immunity and resulting outcomes.
Project 3 develops and tests a new immunization strategy to enhance the induction of cytotoxic lymphocytes
(CTLs) against multiple patient-specific epitopes, by targeting cancer cells, endogenous dendritic cells (DCs)
and ex vivo generated DCs. We will compare the immunopeptidomes on OvCa cells and two populations of
DC specialized in CTL induction: ex-vivo generated alpha-type-1-polarized (αDC1s) and endogenous
conventional DCs (cDC1s) which share the inflammatory BATF3/IRF8 phenotype and elevated ability to
cross-present multiple cancer-cell-associated antigens to CD8+ T cells.
Combining our unique in vitro sensitization (IVS) and bioinformatics approaches, we will test the overall
hypothesis that the mismatch between immunopeptidomes of OvCa cells and DCs presenting antigens
from cancer cells limits the therapeutic effectiveness of spontaneous and vaccination-induced CTL
responses. We further hypothesize that αDC1s loaded with synthetic patient-specific neoantigen peptides
will bypass such mismatch, inducing CTLs particularly effective in killing OvCa tumors. We propose the
following three Aims:
Specific Aim 1: Compare the antigenic specificity of human CD8+ T cells induced by DCs loaded with
autologous OvCa cells, tumor-eluted peptides and patient-specific neoantigen peptides identified by
in-silico approaches. We hypothesize that CTLs induced by autologous cancer cell-loaded DC1s or
cDC1s contain large number of CTLs which are irrelevant for tumor recognition, which deficit can be
corrected by loading DCs with synthetic neoantigen peptides specific to each patient's OvCa cells.
Specific Aim 2: Evaluate the immunopeptidome differences between OvCa cells and tumor-loaded
αDC1s and endogenous cDC1s and test the feasibility of their adjustment. We hypothesize that
immune adjuvants and inflammatory mediators can be used to modulate APM patterns and
immunopeptidomes of DCs and OvCa cells, to enhance the antigenic match between arising CTLs and
autologous OvCa cells.
Specific Aim 3: Determine the feasibility, safety and clinical efficacy of αDC1 vaccines loaded with
patient-specific neoantigen peptides combined with PD-1 blockade. Each patient will receive 8 courses
of DC1 vaccines loaded with patient-specific neoantigens and pembrolizumab. Guided by the results of Aim
2, the patients may also receive systemic immune modulation to increase the visibility of their own OvCa
cells to DC1-induced CTLs and reduce immune suppression. Clinical efficacy will be monitored by iORR.
Predicted Impact: Results of Project 3 will be translated into development of novel therapeutic vaccines and
prospectively into new modes of immune checkpoint inhibition and ado...

## Key facts

- **NIH application ID:** 10473682
- **Project number:** 5P50CA159981-08
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE CORP
- **Principal Investigator:** Pawel Kalinski
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $323,091
- **Award type:** 5
- **Project period:** 2013-09-18 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10473682

## Citation

> US National Institutes of Health, RePORTER application 10473682, IRP-3 (5P50CA159981-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10473682. Licensed CC0.

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