# Precision Delivery and Imaging to Enhance Solid Tumor Therapy

> **NIH NIH P01** · PROTEOGENOMICS RESEARCH INSTIT/SYS/ MED · 2020 · $2,667,097

## Abstract

PROJECT 1 SUMMARY
Existing antibody-based interventions for cancer rely on passive delivery of the circulating 
drug that depends on a large concentration gradient across the semi-permeable wall of 
blood vessels to get inside tumors. The forces driving the drug from the bloodstream into 
tumors result in sub-optimal delivery and poor access to tumor cells, in part because 
endothelial cells (EC) forming the vascular wall constitute a significant, limiting barrier. 
We intend to boost precision delivery into primary and metastatic tumors by overcoming 
the vascular EC barrier through a highly precise, active transport pathway that we 
discovered through proteomic imaging and named the caveolae pumping system. The 
approach proposed here to enhance delivery goes well beyond typical so- called 'active 
targeting' of antibodies. Our lead humanized antibody against Annexin A1 (hAnnA1), a 
tumor- specific antibody concentrated in EC caveolae, not only binds its intended target 
but is actually the first antibody to penetrate solid tumors actively, rapidly and specifically. 
It does so even at very low dosages and reaches unprecedented intra-tumoral 
concentrations well beyond the highest blood levels after injection. It is now time to test 
this unprecedented immunotargeting in humans. We propose here to develop a 
radiolabeled humanized mAnnA1 to detect and destroy primary and metastatic lesions. 
Major aims of this project are to: 1-2) evaluate in vivo delivery and efficacy of novel 
caveolae-targeting radioimmunoconjugates in hard-to-treat metastatic tumor models of 
breast cancer; 3) test the effectiveness of caveolae pumping in human tumor blood 
vessels using PDX and novel human IVM tumor models; and translate hAnnA1 towards 
clinical testing. We will 4) determine here the degree to which caveolae can be targeted 
to pump radiolabeled antibodies across vascular EC to concentrate them inside solid 
tumors as means to improve image-guided drug delivery and enhance 
their efficacy. Antibodies will be provided by Core B and radiolabeled with assistance 
provided by Core D for preclinical work. Several mammary tumor models will be used to 
assess the ability of radiolabeled hAnnA1 to target primary and metastatic tumors via 
imaging services provided in Core C. We will study by intravenously injected hAnnA1 with 
advanced multimodality in vivo imaging to quantify and optimize precision transvascular 
delivery and tumor penetration. As the utility of caveolae targeting in humans requires 
AnnA1 expression in tumor EC caveolae, we will use Core C imaging services to compare 
vascular expression of AnnA1 in preclinical tumor models and human tumors. To translate 
our findings for clinical testing, we will test hAnnA1, humanize further if needed and 
partner with NCI's NExT program for cGMP production, quality control and toxicology of 
hAnnA1. With Core D, Project 3 will optimize hAnnA1 radiolabeling necessary to conduct 
a first-in-human imaging trial ...

## Key facts

- **NIH application ID:** 9974485
- **Project number:** 5P01CA221775-02
- **Recipient organization:** PROTEOGENOMICS RESEARCH INSTIT/SYS/ MED
- **Principal Investigator:** Jan Eugeniusz Schnitzer
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,667,097
- **Award type:** 5
- **Project period:** 2019-07-08 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974485

## Citation

> US National Institutes of Health, RePORTER application 9974485, Precision Delivery and Imaging to Enhance Solid Tumor Therapy (5P01CA221775-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974485. Licensed CC0.

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