# Autologous  Humanized  Mouse  Model  of  Non-Small  Cell  Lung  Cancer (NSCLC) to Investigate the Tumor-Immune Landscape and Its Response to Treatment

> **NIH NIH K08** · YALE UNIVERSITY · 2020 · $148,177

## Abstract

PROJECT SUMMARY
Non-small cell lung cancer (NSCLC) remains the major cause of cancer mortality across the globe, despite
exciting advances in immune-based therapies. These therapies, while dramatically effective in some patients,
are ineffective in the majority of NSCLC patients. The causes of treatment failure remain incompletely understood,
as is the role of the local tumor microenvironment (TME) in influencing tumor growth, both in the presence and
absence of these therapies.
To better study human tumor-immune interactions and immunotherapeutics, we have developed a humanized
mouse model that supports the engraftment of mice bearing a matched human hematopoietic system and tumor
from an individual NSCLC patient. In addition, this model is unique in its support of functional myeloid cells as
part of the innate immune system. We propose to use these autologously-engrafted humanized NSCLC PDX
models to study the TME in detail, employing flow cytometric, immunostaining and single cell genomic analyses
to characterize the transcriptional and proteomic states of the cells present. We will correlate tumor growth to
specific cell populations identified with these methods, enhancing our understanding of the pathways active in
tumor- vs blood-resident immune cells, and identifying established and possibly new networks of immune
dysfunction in the TME. Armed with this knowledge, we will probe the pathways active in these patient models
using drugs specific to the immune exhaustion and tumor promoting mechanisms we identify. Our goal is to gain
a deeper understanding of how the TME and immunotherapeutics interact, and to develop these immune avatar
mice as models that may predict a patient’s response to a particular immunotherapy.
The principal investigator is a physician-scientist, with a PhD in genetics and post-doctoral and clinical training
in Medical Oncology. His career goal is to become an independent investigator studying tumor-immune
interactions. The proposed K08 training plan will provide the candidate with mentorship and coursework to build
the expertise necessary to execute the proposed project and become independent in the field of translational
immuno-oncology.

## Key facts

- **NIH application ID:** 10019482
- **Project number:** 5K08CA245211-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Michael Chiorazzi
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $148,177
- **Award type:** 5
- **Project period:** 2019-09-17 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019482

## Citation

> US National Institutes of Health, RePORTER application 10019482, Autologous  Humanized  Mouse  Model  of  Non-Small  Cell  Lung  Cancer (NSCLC) to Investigate the Tumor-Immune Landscape and Its Response to Treatment (5K08CA245211-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10019482. Licensed CC0.

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