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

Award Number: K08CA245211
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/17/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$3,856 )
2026	2023	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cancer Research Manpower	000	5	11/21/2025	NON-COMPETING CONTINUATION	-$3,856
														Subtotal = -$3,856

Issue Date FY: 2023 ( Subtotal = $148,177 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cancer Research Manpower	000	5	7/28/2023	NON-COMPETING CONTINUATION	$148,177
														Subtotal = $148,177

Issue Date FY: 2022 ( Subtotal = $148,177 )
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cancer Research Manpower	000	4	8/12/2022	NON-COMPETING CONTINUATION	$148,177
														Subtotal = $148,177

Issue Date FY: 2021 ( Subtotal = $148,177 )
2021	2021	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cancer Research Manpower	000	3	8/20/2021	NON-COMPETING CONTINUATION	$148,177
														Subtotal = $148,177

Issue Date FY: 2020 ( Subtotal = $148,177 )
2020	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cancer Research Manpower	000	2	8/27/2020	NON-COMPETING CONTINUATION	$148,177
														Subtotal = $148,177

Issue Date FY: 2019 ( Subtotal = $148,177 )
2019	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cancer Research Manpower	000	1	9/17/2019	NEW	$148,177
														Subtotal = $148,177

Grand Total All Awards = $737,029

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

Award Number: K08CA245211

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/17/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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