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Glial tumor image-guided surgery and treatment

Award Number: R01CA209921
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2022

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Glial tumor image-guided surgery and treatment - ABSTRACT In spite of huge clinical efforts, and a wealth of data on tumor biology, survival from glioma has not significantly changed in the last 25 years. Extent of resection remains the most important determinant of survival for gliomas of all grades. However, the ability to achieve total resection is limited due to the infiltrative nature of gliomas, making it difficult for surgeons to distinguish between tumor and normal brain tissue. Thus, it is important to develop new imaging and drug delivery technologies to specifically image cancer cells during surgical resection, while providing means to focally treat residual tumor deposits interspaced in normal brain. Several strategies have been developed to improve the extent of tumor resection while limiting damage to surrounding brain, including intraoperative MRI and fluorescence imaging. However, these methods suffer from one or several shortcomings, such as lack of light for deep tissue penetration, not actively crossing blood-brain barrier (BBB) and membranes of tumor cells, lack of precise overlap of white light and fluorescence images, and/or time delayed imaging of tumor delineations. A promising recent method is based on Chlorotoxin- Indocyanine Green (ICG) conjugate (BLZ-100, “tumor paint”, presently in phase 1 clinical trial) for improved Targeted NIR Fluorescence Guided Resection (TFGR). However, resection alone will not be sufficient for complete removal of infiltrating glioma cells without sacrificing healthy brain tissue. We hypothesize that our novel glioma targetable imaging and treatment nanoconjugates are able to cross the BBB for guided surgery. We also hypothesize that similar nanoconjugates can effectively eradicate postsurgical remnant glioma cells inhibiting in a dual-pronged fashion the major glioblastoma markers, protein kinase CK2 and epidermal growth factor receptor (EGFR and EGFRvIII mutant). Specific Aim 1. Synthesis and characterization of novel glioma targetable near infrared (NIR) fluorescent imaging agents. Nanoimaging agents PMLA/CTX/ICG and PMLA/CTX/anti-TfRmAb/ICG will be synthesized and studied for producing intensive NIR fluorescence, suitable physico-chemical properties, synthetic reproducibility and stability. Tumor visualization with an optimized device for clinical intra-operative NIR fluorescence imaging will be performed to determine lead nanoconjugate for brain tumor imaging. Specific Aim 2. Synthesis and characterization of nanoconjugates for glioblastoma multiforme treatment. Precise glioma treatment depends on tumor-specific molecular subtype/heterogeneity verified by different molecular markers (CK2 introduced as a novel biomarker, and EGFR/EGFRvIII highly expressed in glioma). Specific Aim 3. Toxicity study of nanoconjugates for brain tumor imaging and treatment. To ensure translation of the results to the clinical trial, the selected lead nanodrugs from in vitro and in vivo efficacy studies must be examined in preparation for IND approval by FDA.


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: 2024 ( Subtotal = $0 )
2024	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	21100 ERWIN ST	WOODLAND HILLS	CA	91367	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	000	6	10/13/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	000	6	11/10/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	004	6	6/14/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2021	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	003	6	5/11/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$23,752
2021	2021	TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION	1018 WESTWOOD BLVD	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	001	6	5/3/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$414,812
2021	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	002	5	5/11/2021	NON-COMPETING CONTINUATION	-$23,752
2021	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	000	5	4/29/2021	NON-COMPETING CONTINUATION	-$414,812
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $511,167 )
2020	2020	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	000	5	5/20/2020	NON-COMPETING CONTINUATION	$511,167
														Subtotal = $511,167

Issue Date FY: 2019 ( Subtotal = $495,835 )
2019	2019	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	000	4	5/10/2019	NON-COMPETING CONTINUATION	$495,835
														Subtotal = $495,835

Issue Date FY: 2018 ( Subtotal = $519,467 )
2018	2018	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	000	3	4/24/2018	NON-COMPETING CONTINUATION	$519,467
														Subtotal = $519,467

Issue Date FY: 2017 ( Subtotal = $523,617 )
2017	2017	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	000	2	5/19/2017	NON-COMPETING CONTINUATION	$523,617
														Subtotal = $523,617

Issue Date FY: 2016 ( Subtotal = $544,935 )
2016	2016	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD, METRO 203	LOS ANGELES	CA	90048	LOS ANGELES	USA	Cancer Detection and Diagnosis Research	000	1	6/13/2016	NEW	$544,935
														Subtotal = $544,935

Grand Total All Awards = $2,595,021

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Glial tumor image-guided surgery and treatment

Award Number: R01CA209921

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2022

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