# Immune modulation of radiation therapy with Flt3 ligand

> **NIH NIH R44** · CELLDEX THERAPEUTICS, INC. · 2021 · $1,631,702

## Abstract

Project Summary
This proposal is a unique collaboration between a small, but full capability biotechnology company
and an academic institution specialized in radiation therapy. Stereotactic radiosurgery (SRS) is being
frequently used to control macroscopic tumor in patients with limited metastases. The success of SRS
in controlling macroscopic disease has generated enthusiasm in combining SRS with systemic agents,
such as, cytotoxic chemotherapeutics and biologically targeted agents for the treatment of early
metastatic cancer. The goal is to treat macroscopic tumor with SRS while systemic chemotherapy
targets microscopic cancer cells. Among systemic therapeutics, immunotherapy has the potential to
be integrated with RT to induce a tumor-specific immune response that could enable the body's own
immune system to target residual and metastatic tumor cells that are not ablated after radiation
therapy alone. Since radiation therapy results in the release of tumor associated antigens from the
dying tumor cells, increasing the number and activity of professional antigen presenting cells such as
dendritic cells could increase the induction of effective tumor immunity. We have shown that
administration of Fms-like tyrosine kinase 3 ligand (Flt3L) significantly increases in the number of
dendritic cells and synergizes with radiation therapy to improve survival in preclinical models of lung
cancer and in preliminary results from a pilot human trial of patients with non-small cell lung cancer.
This proposal aims to broaden these exciting findings by expanding the clinical experience to move
the therapy towards commercialization for greater patient access. The proposal also includes
introduction into the clinical trial of a dendritic cell activating antibody that targets CD40, a pathway
that has been shown to synergize with Flt3L and radiation therapy. To support the clinical study,
clinical grade Fltr3L and the CD40 agonist antibody will be manufactured.

## Key facts

- **NIH application ID:** 10252896
- **Project number:** 5R44CA192435-05
- **Recipient organization:** CELLDEX THERAPEUTICS, INC.
- **Principal Investigator:** Chandan Guha
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,631,702
- **Award type:** 5
- **Project period:** 2015-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10252896

## Citation

> US National Institutes of Health, RePORTER application 10252896, Immune modulation of radiation therapy with Flt3 ligand (5R44CA192435-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10252896. Licensed CC0.

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