# JOC-x: Chemotherapy conjugates that open tumor tight junctions to treat cancer

> **NIH NIH R44** · PAI LIFE SCIENCES, INC. · 2020 · $556,615

## Abstract

PROJECT SUMMARY
A central mechanism of tumor drug resistance is the maintenance of tight junctions between
malignant cells preventing penetration of molecules into the tumor microenvironment. We have
generated junction openers (“JO”) that are small proteins that bind to desmoglein 2 (DSG2), a
junction protein that is overexpressed in many cancers. Intravenous injection of JO increases
tumor penetration and efficacy of many types of cancer therapy. Our studies have shown that the
effective doses of chemotherapy can be reduced when the drugs are combined with JO. JO
accumulates in tumor tissue as much as 100-fold above normal tissues making it a targeting
mechanism to tumors. We have also published that application of JO has not been associated
with toxicities in hDSG2 transgenic mice and that the co-administration of JO and chemotherapy
was well tolerated in non-human primates.
In phase 1 we were able to show that: (1) we can make JOC-x conjugates for a number of cancer
treatment and imaging applications; and (2) that the JOC-x constructs retain their activity in tumor
models. We now are motivated to build on the promising data generated in phase 1 and move
these conjugates towards clinical testing by: (1) Preparing JOC-x for cGMP compliant production
by process development, scaling, and writing manufacturing batch records; (2) Producing JOC-x
conjugates with distinct functionalities to demonstrate utility and flexibility of the platform; and (3)
Testing these JOC-x conjugates in animal models
At the conclusion of the research proposed here we will have produced a conjugatable tumor tight
junction opening candidate that can be used in a number of embodiments. Each of the products
could become stand-alone therapeutics and be developed towards clinical testing.

## Key facts

- **NIH application ID:** 10020907
- **Project number:** 5R44CA206607-03
- **Recipient organization:** PAI LIFE SCIENCES, INC.
- **Principal Investigator:** DARRICK Albert CARTER
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $556,615
- **Award type:** 5
- **Project period:** 2016-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020907

## Citation

> US National Institutes of Health, RePORTER application 10020907, JOC-x: Chemotherapy conjugates that open tumor tight junctions to treat cancer (5R44CA206607-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10020907. Licensed CC0.

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