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Targeting microbial triggers of gammopathy for immunoprevention

Award Number: UG3CA290302
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/13/2024
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Targeting microbial triggers of gammopathy for immunoprevention - Abstract: Multiple myeloma (MM) is an incurable plasma cell tumor preceded by a defined preneoplastic state termed as monoclonal gammopathy of undetermined significance (MGUS). Strategies to effectively intercept/prevent clinical malignancy remain an unmet need and are the focus of this application. Changes in microbial communities have been extensively studied in the context of cancer outcomes and therapy. However, very few causal relationships between specific microbes and human malignancies have been defined, and suitable models to study these interactions are lacking. It is increasingly appreciated that MM/MGUS originate in the setting of prior chronic inflammation and B cell activation, but the underlying triggers remain unknown. This application involves three PIs (Dhodapkar, Flavell, Palm) with complementary expertise and a track record of productive collaboration. The application is based on exciting preliminary data describing the discovery of a commensal microbial species that directly engage several human MM-associated B-cell receptors. This is supported by data from new humanized models to study interactions between the human immune system and microbial communities in vivo. The proposal also utilizes biospecimens from MGUS patients treated with a short course of antibiotics to reduce pathogenic bacteria. Studies proposed in this application will characterize the full spectrum of human gut microbes that can potentially serve as antigenic triggers for human B cells and MGUS. It will also evaluate causal relationships between specific microbes and activation of human B cells as well as MGUS cells utilizing newly developed models. Finally, it will evaluate how microbial manipulation in MGUS patients can impact the inflammatory microenvironment known to be present and implicated in the pathogenesis of MGUS and its transition to clinical malignancy. Together, these studies may lead to novel approaches for immune-prevention of clinical MM by targeting the underlying precursor states such as MGUS. Insights from these studies may also have implications for interactions between specific microbes and human B cells, broadly impacting human autoimmunity and cancer immunotherapy.


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 = $0 )
2026	2025	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	000	2	12/11/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $846,118 )
2025	2025	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Biology Research	001	2	7/28/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$846,118
2025	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cancer Biology Research	000	1	7/28/2025	NEW	$0
2025	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cancer Biology Research	002	1	9/24/2025	NEW	$0
														Subtotal = $846,118

Issue Date FY: 2024 ( Subtotal = $789,579 )
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cancer Biology Research	000	1	6/13/2024	NEW	$789,579
														Subtotal = $789,579

Grand Total All Awards = $1,635,697

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Targeting microbial triggers of gammopathy for immunoprevention

Award Number: UG3CA290302

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 06/13/2024

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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