# Mechanistic study on synergistic photo-immunological effects of laser immunotherapy for metastatic cancers

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA · 2021 · $354,563

## Abstract

Project Summary
Metastasis causes treatment failure and 90% of cancer-related deaths. We have developed laser
immunotherapy (LIT) for the treatment of metastatic cancers. LIT combines local laser photothermal
therapy (PTT) and immunotherapy using glycated chitosan (GC), a novel immunoadjuvant, to induce
systemic antitumor immune responses. LIT has shown success in clinical trials for late-stage, metastatic
cancer patients who had failed conventional treatment modalities. Specifically, LIT has demonstrated its ability
to eliminate treated primary tumors and eradicate untreated metastases at distant sites. However, the
mechanism of LIT, particularly how it controls tumor metastases, has not been fully investigated. Based on our
previous studies, we believe that PTT and GC each induces unique immunological reactions, which, when
synergized, produce a systemic, long-term antitumor immunity. Specifically, we hypothesize that: 1) PTT
induces immunogenic tumor cell death (ICD), providing antigen sources and damage-associated molecular
patterns (DAMPs) to trigger host antitumor immune responses; 2) GC enhances uptake and presentation of
antigens generated by PTT-induced ICD, amplifying antitumor T cell response; and 3) LIT synergizes and
amplifies the immune responses induced by PTT and GC, particularly when combined with other
immunotherapies, such as checkpoint inhibition, providing potent, systemic therapeutic effects, especially on
tumor metastases. To test these hypotheses, we plan to achieve the following aims: (1) to determine the
photothermal-immunological effects of PTT by determining temperature distribution in tumor tissue and by
characterizing the ICD and DAMPs generated by PTT; (2) to determine the effects of GC on immune system
during LIT, particularly on activation of T cell as well as enhancement of antigen uptake and presentation; and
(3) to determine the effects of LIT, as well as the combination of LIT and checkpoint inhibition, on the
enhancement of tumor immunogenicity and on controlling tumor metastasis. The successful completion of this
project will achieve the following goals: (1) to obtain a comprehensive understanding of the immunological
mechanism of LIT in eliminating and inhibiting metastases; (2) to lay the foundation necessary to advance LIT
into an effective treatment modality for patients with a variety of metastatic cancers; (3) to facilitate the
development of new, novel treatment strategies using synergistic immunological mechanisms similar to that of
LIT, in combination with other complementary therapies, for patients with metastatic cancers.

## Key facts

- **NIH application ID:** 10249219
- **Project number:** 5R01CA205348-05
- **Recipient organization:** UNIVERSITY OF OKLAHOMA
- **Principal Investigator:** Wei R. Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $354,563
- **Award type:** 5
- **Project period:** 2017-08-04 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249219

## Citation

> US National Institutes of Health, RePORTER application 10249219, Mechanistic study on synergistic photo-immunological effects of laser immunotherapy for metastatic cancers (5R01CA205348-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10249219. Licensed CC0.

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