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Role of the macrophage derived XL313 epitope in angiogenesis and tumor growth

Award Number: R01CA196739
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/05/2016
PERIOD OF PERFORMANCE END DATE: 11/30/2022

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Role of the macrophage derived XL313 epitope in angiogenesis and tumor growth - Whiles significant progress has been made in the development of new therapeutics to control malignant melanoma, the overall 5-year survival of patients with metastatic disease remains low in the majority of treated subjects. Thus, there is an urgent need for a more detailed understanding of how immune and inflammatory mechanisms govern melanoma progression in order to enhance long-term durable responses in a larger percentage of patients. Evidence indicates that immune infiltrates within the tumor microenvironment such as macrophages play critical roles in angiogenesis, tumor growth and escape from immune control. Melanomas often use an adaptive strategy of actively reprogramming stromal elements towards an immunosuppressive phenotype. Tumor associated macrophages (TAM) can modify both endothelial and T-cell behavior, thereby regulating angiogenesis, tumor growth and the efficacy of many cancer therapies. Identifying novel pro- angiogenic and immune suppressive factors generated by TAMs may provide new therapeutic opportunities and contribute to a more in depth understanding of how the tumor microenvironment controls melanoma growth. To this end, we made the surprising observation that an evolutionarily conserved RGDKGE containing collagen epitope can be generated by M2-like macrophages, and its expression was elevated over 3-fold within the circulation of a cohort of melanoma patients. Remarkably, this RGDKGE collagen epitope, but not other RGD collagen peptides, enhanced endothelial cell growth, stress fiber formation, nuclear translocation of the Yes-associated protein YAP, and induced a dose-dependent angiogenic and pro-inflammatory response in vivo. Based on these and other data, we will test the hypothesis that the RGDKGE epitope regulates angiogenesis and tumor growth by a novel integrin-YAP-dependent mechano-transduction pathway leading to the initiation of a pro-angiogenic signaling program.


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: 2023 ( Subtotal = $0 )
2023	2021	MAINEHEALTH	22 BRAMHALL ST	PORTLAND	ME	04102	CUMBERLAND	USA	Cancer Biology Research	000	5	9/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $356,850 )
2021	2021	MAINEHEALTH	22 BRAMHALL ST	PORTLAND	ME	04102	CUMBERLAND	USA	Cancer Biology Research	000	5	11/6/2020	NON-COMPETING CONTINUATION	$339,007
2021	2021	MAINEHEALTH	22 BRAMHALL ST	PORTLAND	ME	04102	CUMBERLAND	USA	Cancer Biology Research	001	5	1/26/2021	NON-COMPETING CONTINUATION	$17,843
														Subtotal = $356,850

Issue Date FY: 2020 ( Subtotal = $356,850 )
2020	2020	MAINEHEALTH	22 BRAMHALL ST	PORTLAND	ME	04102	CUMBERLAND	USA	Cancer Biology Research	000	4	11/15/2019	NON-COMPETING CONTINUATION	$321,165
2020	2020	MAINEHEALTH	22 BRAMHALL ST	PORTLAND	ME	04102	CUMBERLAND	USA	Cancer Biology Research	001	4	1/14/2020	NON-COMPETING CONTINUATION	$35,685
														Subtotal = $356,850

Issue Date FY: 2019 ( Subtotal = $346,144 )
2019	2019	MAINE MEDICAL CENTER	22 BRAMHALL ST	PORTLAND	ME	04102	CUMBERLAND	USA	Cancer Biology Research	000	3	11/23/2018	NON-COMPETING CONTINUATION	$346,144
														Subtotal = $346,144

Issue Date FY: 2018 ( Subtotal = $356,850 )
2018	2018	MAINE MEDICAL CENTER	22 BRAMHALL ST	PORTLAND	ME	04102	CUMBERLAND	USA	Cancer Biology Research	000	2	11/27/2017	NON-COMPETING CONTINUATION	$321,165
2018	2018	MAINE MEDICAL CENTER	22 BRAMHALL ST	PORTLAND	ME	04102	CUMBERLAND	USA	Cancer Biology Research	001	2	5/23/2018	NON-COMPETING CONTINUATION	$35,685
														Subtotal = $356,850

Issue Date FY: 2017 ( Subtotal = $356,850 )
2017	2017	MAINE MEDICAL CENTER	22 BRAMHALL ST	PORTLAND	ME	04102	CUMBERLAND	USA	Cancer Biology Research	000	1	12/5/2016	NEW	$356,850
														Subtotal = $356,850

Grand Total All Awards = $1,773,544

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Role of the macrophage derived XL313 epitope in angiogenesis and tumor growth

Award Number: R01CA196739

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/05/2016

PERIOD OF PERFORMANCE END DATE: 11/30/2022

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