# Evaluation of lead FANA oligos targeting FOXP3, with and without anti-PD-1 mAb, as an approach for cancer immunotherapy

> **NIH NIH R43** · AUM LIFETECH, INC. · 2022 · $400,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Lung cancer accounts for >25% of cancer-related deaths in both men and women, making it the largest
source of cancer-related mortality. Despite advancements in surgical intervention, radiation, chemotherapy,
and immunotherapy, the 5-year survival rate for all types of lung cancer is 19%. The advent of immune
checkpoint inhibitor therapy is associated with remarkable efficacy is some patients with lung cancers, but
>75% of patients do not achieve meaningful clinical responses. Currently, T-regulatory (Treg) T cells are
regarded as one of the major obstacles to the successful clinical application of tumor immunotherapy. Tregs
contribute to the early establishment and progression of tumors, dampen effector cell responses by various
mechanisms, and promote and support pro-tumoral myeloid-derived suppressor cell development and
function. Tregs are thereby key to the immunosuppressive state of the tumor microenvironment that
prevents effective anti-tumor immune responses. Pre-clinical studies show targeting of Tregs, by their
depletion or functional modulation, can have significant therapeutic benefit, alone or in combination with
other immunomodulatory approaches. We and others have described the significant accumulation of
intratumoral Treg in lung cancer patients, and their increased intratumoral numbers correlate with poor
prognosis in many types of cancers.
Tregs are defined by their expression of the transcription factor FOXP3, which controls Treg development,
stability, and function. FOXP3 is the key element of multiple Treg-associated molecular complexes that
regulate the Treg-specific gene network and mechanisms of Treg-mediated immune regulation. FOXP3 is
located intracellularly, and previous efforts to target Tregs using their CD25 surface marker have
unintentionally co-targeted CD25+ activated T effector cells, causing a lack of robust anti-tumoral
efficiency in pre-clinical and clinical studies, along with severe adverse effects and toxicity. On the other
hand, Foxp3-specific depletion of Treg using tumor bearing DEREG transgenic mice, in combination with
anti-tumor vaccine therapy, resulted in robust antitumor immunity and an absence of overt autoimmunity.
Thus, there is an urgent and unmet need for therapies that can selectively target Treg cells, allowing the
body to mount its normal defenses against the cancer, without negative influences on the rest of the immune
system.
We have developed third generation FANA antisense oligonucleotides (FANA ASOs) that selectively
inhibit Tregs by knockdown of FOXP3 expression. This next generation of ASO differs from their
predecessors by chemical modifications that allow their efficient (gymnotic) self-delivery, even to resting
cells, and make them resistant to degradation by endogenous nucleases. In preliminary studies, anti-Foxp3
FANA ASOs reduced Foxp3 expression and suppressive functions of murine Tregs, and in 50% of
syngeneic mice bearing lung tumors, daily injection ...

## Key facts

- **NIH application ID:** 10546343
- **Project number:** 1R43CA275470-01
- **Recipient organization:** AUM LIFETECH, INC.
- **Principal Investigator:** Veenu Aishwarya
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,000
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10546343

## Citation

> US National Institutes of Health, RePORTER application 10546343, Evaluation of lead FANA oligos targeting FOXP3, with and without anti-PD-1 mAb, as an approach for cancer immunotherapy (1R43CA275470-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10546343. Licensed CC0.

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