# Development of CA-IL-12 for Triple Negative Breast Cancer

> **NIH NIH R44** · CYTONUS THERAPEUTICS, INC. · 2024 · $893,673

## Abstract

Most cancer patients die as a result of metastatic disease and our inability to effectively deliver therapeutic drugs into the
anatomical niches where cancer cells thrive. Thus, there is a major unmet need to develop therapeutic strategies that
effectively target cancer cells in the local tumor microenvironment (TME) while minimizing peripheral toxicity. Cytonus
Therapeutics and UCSD Moores Cancer Center has co-developed a highly innovative first-in-class drug transporter platform
(CargocytesTM) that is a safe and effective means to deliver therapeutic drugs to treat primary and secondary tumors.
Cargocytes possess several unique features that we leverage for precision delivery of cancer therapeutics to patients with
metastatic disease. First, Cargocytes possess innate tumor trophic properties and are engineered with additional homing
controls that allow for precise, predictable, and safe delivery of therapeutic cargo to the TME. Moreover, because they lack
a rigid nucleus, they clear critical FDA barriers to safety due to their inability to transfer or inappropriately express genomic
DNA. In addition, they are smaller and more malleable than nucleated carriers and better able to penetrate deep within
tumor tissue and metastatic foci. Furthermore, they retain all biosynthetic machinery and can express biological cargo within
the TME. While Cargocytes can deliver a wide range of therapeutic cargoes, they are ideally suited for locally delivering
potent immune activating agents, such as IL-12, into the immunologically “cold” TME.
Our phase I proof-of-concept work shows that Cargocytes precisely deliver IL-12 into the TME, deeply penetrating and
interdigitating within metastatic foci when delivered intratumorally or systemically and resulting in a dramatic reduction in
metastatic burden that can be measured within 24 hours. While this was demonstrated using Cargocytes that secrete IL-12
(CA-IL-12), we have since focused on development of Cargocytes for intravenous delivery, a more desirable administration
route for clinical development and treatment of systemic metastatic disease. Therefore, Phase II work will evaluate the
potential of intravenously administered Cargocytes to deliver secreted (CA-IL-12) or surface contained (CA-scIL-12) to
breast cancers that have metastasized to lungs or liver. Our hypothesis is that Cargocytes will home to metastases, deliver
IL-12 deep within disease foci, and break immune tolerance when used in combination with ICB. This will lead to i) local
and systemic antitumor immunity, ii) a reduction in metastatic burden, iii) improved tumor-free and overall survival, and
iv) durable antitumor immunity. Three specific aims are outlined to test this hypothesis. Aim 1 will determine the abilities
of peripherally administered CA-scIL-12 and CA-IL-12 to locally deliver IL-12 to primary and secondary tumors and to
reprogram innate and adaptive anti-tumor immune responses. Aim 2 will then evaluate the ability of our lead CA-IL-...

## Key facts

- **NIH application ID:** 10917204
- **Project number:** 5R44CA250887-03
- **Recipient organization:** CYTONUS THERAPEUTICS, INC.
- **Principal Investigator:** EDWARD J FILARDO
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $893,673
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917204

## Citation

> US National Institutes of Health, RePORTER application 10917204, Development of CA-IL-12 for Triple Negative Breast Cancer (5R44CA250887-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10917204. Licensed CC0.

---

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