# Development of novel protein-based therapeutics for lung cancer

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $563,856

## Abstract

Lung cancer is the leading cause of cancer deaths worldwide. The most prevalent type of lung cancer is Non-
Small Cell Lung Cancer (NSCLC). The goal of this application is to implement a collaborative effort involving
preclinical models, bioengineering and functional genomics to further characterize and validate a novel “first in
class” therapeutic strategy for the treatment of lung cancer. Our prior published work and extensive
preliminary data indicates that blockade of CLCF1-CNTFR signaling represents a unique and previously
unexplored approach for lung cancer therapy. The Sweet-Cordero and Cochran laboratories have
collaborated extensively over the past several years to validate this signaling axis, first with shRNA genetic
approaches, and now through the development of an engineered CNTFR receptor decoy (eCNTFR). In Aim 1,
we will further develop eCNTFR as a therapeutic candidate by measuring its thermal and proteolytic stability,
potential for immunogenicity and toxicity, manufacturability, and pharmacokinetics, and will optimize these
properties as needed. We will also perform structural analysis of eCNTFR in complex with CLCF1 to define
high affinity binding characteristics. Lastly, we will test eCNTFR for therapeutic efficacy across a wide array of
preclinical models of NSCLC including human cell lines and patient-derived xenografts. In Aim 2, we will
perform in vitro biochemical assays to fully define the cell-autonomous mechanism of action of eCNTFR
blockade. To further understand the mechanism of action of eCNTFR in vivo, we will complement xenograft
models with a well-characterized genetically engineered mouse model of lung cancer. Importantly, this model
will allow us to study the effects of eCNTFR not only on tumor cells but also on the microenvironment, and to
assess whether eCNTFR has immunomodulatory effects. In Aim 3, we will identify the most effective
combination approaches to enhance eCNTFR therapy. These efforts will be carried out in a rational and
unbiased manner by leveraging CRISPR/CAS9 using a library directed specifically at the targets of FDA
approved drugs. Candidate combination therapies will then be tested in animal models. Our studies will
elucidate critical biological underpinnings of this ligand/receptor signaling axis, and will provide preclinical
validation of an innovative strategy for targeting lung cancer to warrant its further clinical development.

## Key facts

- **NIH application ID:** 10133002
- **Project number:** 5R01CA225103-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** MICHAEL C BASSIK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $563,856
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133002

## Citation

> US National Institutes of Health, RePORTER application 10133002, Development of novel protein-based therapeutics for lung cancer (5R01CA225103-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133002. Licensed CC0.

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