# Molecular engineering and systematic evaluation of bispecific aptamers to develop potent and efficacious therapies for the immunomodulation of Non-Small Cell Lung Cancer

> **NIH NIH F30** · UNIVERSITY OF MISSOURI-COLUMBIA · 2024 · $34,658

## Abstract

PROJECT SUMMARY
Cancer is set to bypass cardiovascular disease as the number one cause of death in United States and it is a
leading cause of death worldwide. Non-Small Cell Lung Cancer (NSCLC) is a major contributing factor to this
statistic. Recent advancements in chemotherapeutic delivery and the development small molecule inhibitors,
such as tyrosine kinase inhibitors, have been indispensable in decreasing disease prevalence and burden.
Additionally, the recent FDA approvals of immunomodulating therapies, such as immune checkpoint inhibitors
(ICIs), chimeric antigen receptor (CAR) T cells, and bispecific antibodies, emphasizes the importance that
immune system evasion plays in disease progression and relapse. Unfortunately, administration of these
targeted and immunomodulating therapies is often met with tumor acquired resistance (e.g., secondary
mutations; T cell exhaustion) and incites non-specific or on-target/off tumor side effects (e.g., immune related
adverse events). This suggests a need for alternative or adjuvant NSCLC therapies that are not only potent and
efficacious but exercise a wide therapeutic index. We propose to exploit aptamer technology as one potential
way to address this need. Aptamers are single strand oligonucleotides that bind to their targets with high
specificity and affinity and their relative lack of immunogenicity as a foreign substance, compared to antibodies,
make them ideal reagents to modulate the immune system. Furthermore, their ease of manipulation makes
molecular engineering to design and optimize such reagents relatively straightforward. Our goal is to develop
novel immunomodulating bispecific aptamers (bsApts) that dually bind to immune cell CD3ε and NSCLC tumor
associated antigens (TAAs) to induce formation of effective immune synapses. We propose to use molecular
engineering techniques to rationally design bsApts and systematically evaluate specific bsApt properties, such
as (i) valency, (ii) affinity, and (iii) linker length/type in their ability to induce artificial immune cell activation in
vitro and anti-tumor responses in vivo. We also propose to take a transcriptomics approach to better understand
how designs/targets affect tumor heterogeneity, tumor infiltrating lymphocyte phenotypes, and off-target immune
cell activation. Secondary goals look at improving pharmacokinetic properties that limit bsApt clinical
translatability while long-term goals look to generalize our findings on these properties to current and future
bispecific therapies that target a wide range of solid and hematological cancers.

## Key facts

- **NIH application ID:** 10918084
- **Project number:** 5F30CA275349-02
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Brian J Thomas
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $34,658
- **Award type:** 5
- **Project period:** 2023-08-21 → 2027-08-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918084

## Citation

> US National Institutes of Health, RePORTER application 10918084, Molecular engineering and systematic evaluation of bispecific aptamers to develop potent and efficacious therapies for the immunomodulation of Non-Small Cell Lung Cancer (5F30CA275349-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10918084. Licensed CC0.

---

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