# Flt3l gene-modified cDC1 in situ vaccination in NSCLC: mechanisms and therapeutic application

> **NIH VA IK2** · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · 2023 · —

## Abstract

PROJECT SUMMARY/ABSTRACT
 Dr. Salehi-Rad is a Staff Pulmonologist at the VA Greater Los Angeles Healthcare System (VA GLAHS)
with a clinical and research interest in lung cancer, the leading cause of cancer death among U.S. Veterans. In
applying for the VA Career Development Award (CDA-2), Dr. Salehi-Rad’s goal is to establish an independent
translational research program at the VA GLAHS, focused on improving our understanding of the
immunopathogenesis of lung cancer for the development of novel approaches for cancer immunotherapy. He is
supported by Steven Dubinett, MD (Primary-Mentor), a renowned VA Merit-funded physician-scientist and a
leading expert in lung cancer, Antoni Ribas, MD, PhD (Co-Mentor), an internationally recognized authority in
cancer immunology, and Paul Boutros, PhD (Co-mentor), a distinguished data scientist. Mentors were identified
based on their complementary scientific expertise for the proposed research and their extensive experience in
mentoring academic physician-scientists. Through UCLA Clinical and Translational Science Institute (CTSI), Dr.
Salehi-Rad will have access to numerous career development seminars that address such topics as grant
writing, manuscript preparation, and ethical research. He will also take graduate courses to obtain further training
in immunology and bioinformatics. Dr. Salehi-Rad will have the full institutional support of both the VA and UCLA
Health Systems to carry out his research.
 Dr. Salehi-Rad has established clinically relevant murine models of NSCLC with increased mutational
burden and identified a novel targetable mechanism of resistance to immunotherapy in LKB1-deficient NSCLC.
Utilizing these murine models, Dr. Salehi-Rad has shown that in situ vaccination (ISV) with elite antigen cross-
presenting conventional type 1 DCs that are gene-modified to secrete FMS-like tyrosine kinase 3 ligand (FLT3L-
cDC1), a cytokine that promotes DC viability and expansion, sensitize immune refractory NSCLC to immune
checkpoint inhibition (ICI). In this proposal, Dr. Salehi-Rad aims to study the immune mechanisms of DC ISV.
Aim 1.1 builds on preliminary in vitro data indicating enhanced viability of FLT3L-cDC1 compared to cDC1 and
seeks to determine the molecular mechanisms that result in increased survival of FTL3L-cDC1. Aim 1.2 & 1.3
utilize various murine models to determine the vaccine and endogenous DC viability, antigen trafficking and
antigen-specific T cell priming following DC ISV. Aim 2 of the proposal focuses on elucidating the immune
determinants of response to DC ISV as monotherapy or as a combination therapy with ICI. Aim 2.1 & 2.2
combine single cell immunophenotyping by flow cytometry and single cell RNA-sequencing (scRNA-seq) with
spatial analysis by multiplex immunofluorescence (MIF) to develop a comprehensive understanding of the local
and systemic immune responses induced by DC ISV. Aim 2.3 utilizes antibody depletion studies to evaluate the
dependency of DC ISV on T cells and na...

## Key facts

- **NIH application ID:** 10585591
- **Project number:** 1IK2BX006194-01
- **Recipient organization:** VA GREATER LOS ANGELES HEALTHCARE SYSTEM
- **Principal Investigator:** Ramin Salehi-Rad
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10585591

## Citation

> US National Institutes of Health, RePORTER application 10585591, Flt3l gene-modified cDC1 in situ vaccination in NSCLC: mechanisms and therapeutic application (1IK2BX006194-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10585591. Licensed CC0.

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