# Photodynamic therapy with prior inhibition of epidermal growth factor receptor to stimulate antitumor innate immune response

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $444,397

## Abstract

PROJECT SUMMARY/ABSTRACT
Inhibition
remarkably
clinical
with
most
priming
therapy,
of epidermal growth factor receptor (EGFR) prior to the delivery of photodynamic therapy (PDT) can
improve treatment efficacy in animal models of non-small cell lung cancer (NSCLC). Currently,
use of EGFR tyrosine kinase inhibitors (TKIs) for treatment of patients with NSCLC is limited to those
 EGFR mutated disease. EGFR-TKI therapy is typically continued until time of disease progression since
patients eventually develop EGFR-TKI resistant disease. Here, we propose to use EGFR-TKIs as a brief,
therapy for several days rather than as a daily continuous therapeutic. Importantly, as a priming
we hypothesize thatEGFR-TKI pretreatment will improve the therapeutic efficacy of PDT (and ionizing
radiotherapy, XRT) through an innate immune response-dependent mechanism.
the
EGFR
EGFR-TKI
priming
involve
EGFR-TKIs
damage
Indeed,
demonstrate
TKI/PDT).
lymphocytes
cells)
innate
notwithstanding
investigate
clinical
XRT.
vascular
augments
and
demonstrate
Significantly, we posit that
use of EGFR-TKIs as a priming approach to stimulate innate immunity is relevant to patients with
wild-type disease. However, its potential efficacy may not be apparent in the setting of daily continuous
therapy due to suppression of innate and adaptive immunity by prolonged use of EGFR-TKIs. As a
therapy, EGFR-TKIs could augment responses to PDT and XRT through multiple mechanisms that
cooperation between the EGFR-TKIs and PDT or XRT to promote tumor-directed innate immunity.
may increase neutrophil activation in tumors receiving PDT or XRT, serving to increase vascular
and/or stimulate other cells of the innate immune system, such as innate immune lymphocytes.
our published data show EGFR-TKI to increase vascular damage to PDT, and preliminary data
increases in tumor-localized neutrophil activation when PDT is preceded by EGFR-TKI (EGFR-
Additionally, EGFR-TKIs and PDT or XRT may cooperatively increase numbers of innate immune
and the immunologic visibility of target cells (e.g., tumor cells or tumor-associated endothelial
 to these lymphocytes. In fact, in preliminary data the efficacy of EGFR-TKI/PDT is dependent on the
immune lymphocytes NK and  T cells. We note that the role of  T cells in response to EGFR-TKI,
combinations with PDT or XRT, is a novel area of investigation. Moreover, we uniquely
EGFR-TKI priming with proton XRT. Knowledge gained from this proposal will guide selection of a
approach to EGFR-TKI priming with radiation therapy, whether it be with PDT, photon XRT, or proton
Toward this goal, we will address the following aims: To define the role of neutrophils in promoting
damage when PDT is preceded by EGFR-TKI. To ascertain how pretreatment with EGFR-TKI
the response of innate immune l ymphocytes to PDT-treated tumors. To establish the efficacy
innate immune effects of EGFR-TKIs combined with ionizing radiation therapies (photon and proton) and
application in control of lung ...

## Key facts

- **NIH application ID:** 9841929
- **Project number:** 5R01CA236362-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Theresa M Busch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $444,397
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841929

## Citation

> US National Institutes of Health, RePORTER application 9841929, Photodynamic therapy with prior inhibition of epidermal growth factor receptor to stimulate antitumor innate immune response (5R01CA236362-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9841929. Licensed CC0.

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