# Potentiation of Immunotherapy with targeted nanoporphyrin in bladder cancer

> **NIH VA I01** · VA BOSTON HEALTH CARE SYSTEM · 2020 · —

## Abstract

ABSTRACT
Bladder cancer (BCa) is one of the most common cancers in veterans. There is no significant improvement in
overall survival for advanced BCa over the last three decades. Immunotherapy with immune checkpoint
inhibitors showed promising anti-tumor activity in this disease. However, less than 20% of patients respond
to this treatment. Various strategies, including combination with other therapies, are being explored to
enhance the efficacy of immunotherapy. With the funding of the VA Career Development Award-2 and VA
Merit, we developed a BCa-specific PLZ4-nanoporphyrin (PNP) that combines imaging-guided
chemotherapy, photodynamic and photothermal therapies into a single platform. All three therapies have
been shown to potentiate immunotherapy with cancer vaccines. Here we propose to determine whether the
efficacy of immunotherapy with an immune checkpoint inhibitor can be enhanced via combining
immunotherapy with chemotherapy, photodynamic and photothermal therapies using PNP. Because PNP can
target the mouse BCa cell line MB49, we will first conduct the efficacy studies in immunocompetent mice
carrying MB49 syngeneic tumors.
Recently, we developed
humanized mice in which the immune cells of the
host mice are derived from humans. We will implant into these mice patient-derived xenografts (PDX) that are
developed from unselected and uncultured human patient cancer tissues in order to validate the MB49 cell
line studies in mice. We will then translate the studies into BCa transgenic mice to determine whether PNP
can potentiate immunotherapy. Mechanisms of resistance will also be studied. Since we have already held a
pre-IND (Investigational New Drug) consultation with the US Food and Drug Administration for PNP,
successful completion of this project can lead to a clinical trial to combine PNP with immunotherapy in BCa.

## Key facts

- **NIH application ID:** 9898243
- **Project number:** 5I01BX003840-04
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** CHONG-XIAN PAN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898243

## Citation

> US National Institutes of Health, RePORTER application 9898243, Potentiation of Immunotherapy with targeted nanoporphyrin in bladder cancer (5I01BX003840-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9898243. Licensed CC0.

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