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LGR5 antibody drug conjugate for the treatment of neuroblastoma

Award Number: R21CA267381
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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LGR5 antibody drug conjugate for the treatment of neuroblastoma - Neuroblastoma (NB) is a cancer of the nervous system outside the brain that occurs in children under 15 years of age. It is the most frequently diagnosed cancer during infancy, accounting for ~12% of all-cancer related death in children. It is considered a rare cancer since its overall incidence is significantly less than 6 per 100,000 people in the U.S. Approximately half of NB cases are cured with minimal and sometimes no chemotherapy while the other half are high-risk patients who only have a long-term survival of ~50% despite intensive multimodal treatment that is quite toxic. Antibody–drug conjugates (ADCs) are monoclonal antibodies (mAbs) that are covalently linked to cell-killing cytotoxins to deliver the payloads into cancers cells. Multiple ADCs have now been approved by FDA for cancer treatment, including leukemia, breast cancer, and bladder cancer. LGR5 (leucine-rich repeat containing, G protein-coupled receptor 5) is a membrane receptor that is associated with formation and metastasis of cancers in the gastrointestinal system. Therapeutic agents targeting LGR5 and its associated pathway are being developed for gastrointestinal cancers driven by this mechanism. Remarkably, high levels of LGR5 are found in NB tumor cells, and more LGR5 expression is correlated with poor survival. However, whether LGR5 can also be targeted for the treatment of high-risk NBs remains unknown. We have found that ablation of LGR5 from NB cancer cells led to drastic decrease in cancer cell growth in cell cultures and tumor formation in animals. We also generated an ADC using an anti-LGR5 antibody and found that the LGR5 ADC is highly effectively in killing NB cancer cells with high level of LGR5. The goals of this project are to validate LGR5 as a potential target for the treatment of high-risk NBs using the ADC approach and further improve the potency and efficacy of LGR5 ADC. We will generate a series of ADCs with different payloads and determine their activities in blocking tumor growth in animal models. The project, if successful, may lead to the validation of a new approach for the discovery and development of treatments of high-risk NBs and drug candidates for further development.


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: 2025 ( Subtotal = -$71 )
2025	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	2	4/4/2025	NON-COMPETING CONTINUATION	-$71
														Subtotal = -$71

Issue Date FY: 2023 ( Subtotal = $214,414 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	005	2	3/15/2023	NON-COMPETING CONTINUATION	$17,503
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	003	2	11/28/2022	NON-COMPETING CONTINUATION	-$196,911
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	004	2	11/29/2022	NON-COMPETING CONTINUATION	$196,911
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	2	11/15/2022	NON-COMPETING CONTINUATION	$196,911
2023	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	001	1	11/21/2022	NEW	-$182,325
2023	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	002	1	11/22/2022	NEW	$182,325
														Subtotal = $214,414

Issue Date FY: 2022 ( Subtotal = $182,325 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	1	11/26/2021	NEW	$182,325
														Subtotal = $182,325

Grand Total All Awards = $396,668

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LGR5 antibody drug conjugate for the treatment of neuroblastoma

Award Number: R21CA267381

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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