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

> **NIH NIH R41** · CYTONUS THERAPEUTICS, INC. · 2020 · $386,586

## Abstract

Among the 1.7 million new cases of breast cancer diagnosed globally each year, 15-20% are
triple-negative breast cancer (TNBC), which has an aggressive phenotype with high metastatic
capability and poor prognosis. However, current therapeutics for TNBC have unpredictable
efficacy, poor biomarker availability, serious side effects, and the development of treatment
resistance. The goal of this proposal is to develop our Cargocyte'" technology (patents pending)
to improve immune-oncology treatment in patients with TNBC by achieving the safe, non-toxic,
targeted, and transient delivery of interleukin 12 (IL-12). IL-12 is a potent inflammatory cytokine
and immune activator that attracted significant clinical interest because of its ability to induce a
durable anti-tumor response in pre-clinical studies. However, initial clinical development was
halted because systemic administration of IL-12 was associated with high levels of systemic
toxicity, low response rates, and a narrow therapeutic window. Cargocytes possess unique
advantages that facilitate delivery of IL-12 to the tumor microenvironment. They are transfected
with IL-12 mRNAs that transform Cargocytes into cell-like factories producing high levels of
secreted, bioactive, heterodimeric IL-12 cytokine (CA-IL-12). Compared with passive
mechanisms of IL-12 delivery (purified IL-12 cytokine or mRNA, nanoparticles, exosomes etc.),
Cargocytes deliver CA-IL-12 to the tumor microenvironment using multiple active cellular
mechanisms that uniquely transform the tumor microenvironment from immunologically cold to
hot. Furthermore, Cargocytes are tumor trophic and adhere to extracellular matrix (ECM)
proteins within the tumor environment, which improves tumor retention and local CA-IL-12
delivery following IT administration. The proposed research in phase I will focus on (Aim 1)
evaluating the ability of IT CA-IL-12 in combination with PD-1/PD-Ll immune checkpoint
inhibition to target cancer progression using a stringent 4Tl murine orthotopic model of
metastatic TNBC. Aim 2 will evaluate CA-IL-12/PD-Ll safety and toxicity in preparation for a
type C pre-IND meeting using the 4Tl orthotopic model of metastatic TNBC. Following
completion of these studies and guidance discussions with FDA regulatory personnel, further
IND enabling work will be pursued by a phase II STTR proposal to develop CA-IL-12 for clinical
applications.

## Key facts

- **NIH application ID:** 10008177
- **Project number:** 1R41CA250887-01
- **Recipient organization:** CYTONUS THERAPEUTICS, INC.
- **Principal Investigator:** Richard L. Klemke
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,586
- **Award type:** 1
- **Project period:** 2020-06-15 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10008177

## Citation

> US National Institutes of Health, RePORTER application 10008177, Development of CA-IL-12 for Triple Negative Breast Cancer (1R41CA250887-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10008177. Licensed CC0.

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