# Platelets-Mediated Delivery of Checkpoint Inhibitors for Post-Surgical Cancer Immunotherapy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $419,793

## Abstract

PROJECT SUMMARY
Despite continual improvements in surgical techniques, cancer recurrence after surgical resection remains a
significant challenge in cancer therapy. It has also been verified that surgery can induce promotion of cancer
metastasis. In this proposal, utilizing platelet as a delivery vehicle, the team intends to develop a
transformative platform for locally releasing immune checkpoint inhibitors toward post-surgical eradication of
residual cancer cells. In a preliminary study, using the B16F10 melanoma tumor-bearing C57BL/6 mouse
model, it has been demonstrated that the anti-PDL1 (aPDL1) attached platelets (designated P-aPDL1) could
facilitate the accumulation of aPDL1 toward the surgical bed where the residual microtumors remain.
Importantly, the loaded aPDL1 can be effectively released from the activated platelets mediated by the
platelet-derived microparticles (PMPs) upon in situ platelet activation. Moreover, platelets can generate a
local inflamed tumor microenvironment, which could boost T cells activity as well as other immune cells. Here,
the team proposes to further substantiate, optimize and extend the capability of platelets as a delivery platform
for checkpoints blockade-based cancer immunotherapy. The team will validate the detailed treatment
mechanism of P-aPDL1 as well as optimize its physicochemical property. The capability of P-aPDL1 for
treating circulating tumor cells (CTCs) will also be evaluated. In addition, the team will evaluate the potential
of platelets to achieve combination delivery of aPDL1 and gemcitabine (GEM), which can upregulate both
PDL1 and PD1 on tumor cells and tumor infiltrating immune cells, respectively. Furthermore, the twam will
extend this platform to co-deliver different “cells”- therapeutics-loaded platelets and specific chimeric antigen
receptor (CAR) T cells. Three aims will be pursued: in Aim 1, the capability of platelets for delivering
checkpoint inhibitors will be validated and optimized; in Aim 2, the effectiveness of combination delivery of
aPDL1 and GEM using platelets will be evaluated; in Aim 3, the innovative combination cell immunotherapy
with platelets and CAR-T cells will be developed and assessed. The synergistic immune responses as well
as systemic toxicity of this combination cells-based immunotherapy will be evaluated. The proposed research,
when successfully demonstrated in human studies, would significantly enhance the anticancer efficacy and
improving the patients’ survival. This novel in situ bio-responsive strategy may also inspire new treatments
applying bio-particulates for targeting and bio-responsive release of therapeutics.

## Key facts

- **NIH application ID:** 9963190
- **Project number:** 5R01CA234343-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Song Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $419,793
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963190

## Citation

> US National Institutes of Health, RePORTER application 9963190, Platelets-Mediated Delivery of Checkpoint Inhibitors for Post-Surgical Cancer Immunotherapy (5R01CA234343-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9963190. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*