# Transport of Effector T cells and Nano-DC vaccine in Breast Cancer

> **NIH NIH U54** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2020 · $446,417

## Abstract

PROJECT 1 – SUMMARY 
Uncontrolled tumor growth (cancer) often results as a consequence of a patient's ineffective immune 
responses against the tumor. Cancer immunotherapy aims at restoring the body's defense system with tumor- 
specific immune responses. Since dendritic cells (DCs) are professional antigen-presenting cells that can 
process and present tumor antigen to T cells to initiate immune responses, DC vaccines are the natural choice 
for therapeutic intervention. Approval by the US Food and Drug Administration of sipuleucel-T, a DC vaccine for 
advanced prostate cancer, represented a major milestone in this promising field. A DC vaccine is usually 
comprised of DCs internalized with tumor antigens and adjuvants. A sequence of physical and biological events 
determine the success of a functional DC vaccine to elicit the proper immune responses: 1) The DC vaccine 
must migrate from the injection site to lymphoid tissues; 2) The DC vaccine must maintain a mature stimulatory 
status to persistently process and present the immunizing antigen to T cells; and 3) The antigen-specific T cells 
must travel to the tumor-bearing organ and infiltrate into the tumor microenvironment to exert their anti-tumor 
activity. However, these events are often insurmountable hurdles for most DC vaccines thus far. Clinical studies 
have shown that only less than 5% of intradermally injected DCs can reach the lymph nodes. In addition, the 
stimulatory signals of ex vivo matured DCs cannot be maintained in vivo. Furthermore, the tumor 
microenvironment prevents infiltration of the cytotoxic T cells. Therefore, overcoming these sequential barriers 
is critical to the development of a successful therapeutic DC vaccine, in order to facilitate effective transport of 
the DC vaccine and activated T cells. For Project 1 of the Center for Immunotherapeutic Transport 
Oncophysics (CITO), we hypothesize that successful negotiation of the sequential physical and biological 
barriers determines accumulation of DC vaccine in the lymph nodes, especially the tumor-draining lymph nodes. 
Also, modification of the tumor microenvironment facilitates transport of the effector T cells and macromolecular 
drugs that synergize with the Nano-DC vaccine for effective cancer therapy. We have developed a HER2-specific 
Nano-DC vaccine to test the hypothesis. The cell surface HER2 protein is expressed in approximately 20-30% 
of breast cancers and also in many pancreatic cancer patients. We have recently developed a porous silicon 
microparticle (PSM)-based platform for DC vaccine (Nano-DC vaccine) development, and demonstrated that 
PSM could serve both as a reservoir for the tumor antigen and as an adjuvant to stimulate the DC cells. We will 
apply the Nano-DC vaccine platform in this study, and will test our hypothesis in murine models of breast cancer. 
The project will be tightly integrated with the Transport Oncophysics Core (TOC) hinging on its imaging, 
quantification, analysis, an...

## Key facts

- **NIH application ID:** 9997895
- **Project number:** 5U54CA210181-05
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** Rongfu Wang
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $446,417
- **Award type:** 5
- **Project period:** 2016-08-29 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997895

## Citation

> US National Institutes of Health, RePORTER application 9997895, Transport of Effector T cells and Nano-DC vaccine in Breast Cancer (5U54CA210181-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9997895. Licensed CC0.

---

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