Friday, April 26, 2024 4/26/2024

Validating Rapid Microfluidic Isolation of Personalized Aptamers for Monitoring Minimal Residual Disease in Multiple Myeloma

Award Number: R33CA196470
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

¿ DESCRIPTION (provided by applicant): Multiple myeloma (MM) is a plasma cell derived blood cancer that produces monoclonal immunoglobulins (M-Ig). Detection of minimal residual disease (MRD) is of great importance for MM care. All methods used for MRD detection are based on evaluation of plasma cells obtained from bone marrow (BM) biopsies. These methods are susceptible to failure and do not allow frequent monitoring because of their invasiveness. Detection of MRD in peripheral blood is most ideal but remains an unmet medical challenge. Circulating M-Ig proteins are the hallmark of MM, and their detection by currently available serum-based methods, including serum protein electrophoresis (SPEP) and immunofixation (IFE), is used in diagnosis and follow-up, but not MRD monitoring due to insufficient sensitivity. This problem can be addressed by exploiting variable regions (called "idiotypes") of M-Ig proteins, which are tumor-specific and unique to the patient. The ability to monitor the presence and reappearance of the same idiotype in blood after therapy would lead to sensitive MRD detection. This can be enabled by idiotype-targeting aptamers as personalized reagents. Aptamers are single-stranded oligonucleotides that specifically bind to targets, and have been demonstrated to allow sensitive serum-based detection of analytes including immunoglobulins. Through an in vitro process termed systematic evolution of ligands by exponential enrichment (SELEX), aptamers are generated from randomized libraries of oligonucleotides. MRD detection requires generation of aptamers targeting the unique idiotype of the patient. This is impractical with conventional SELEX methods that are labor-intensive and time-consuming, but can be enabled by our innovative microfluidic technology that allows rapid generation of aptamers. Our preliminary microfluidic devices have demonstrated the capability of completing the SELEX process within ~10 hours for successful isolation of immunoglobulin-targeting aptamers. Our long-term objective is to realize a paradigm for sensitive detection MRD in peripheral blood using personalized aptamers targeting patient- and tumor-specific idiotypes of M-Ig proteins of individual MM patients. The goal of this project is to validate the ability of our microfluidic technology to rapidly generate idiotype- targeting aptamers for individual patients for sensitive MRD detection in peripheral blood. We will first optimize a SELEX protocol using readily available IgG1/kappa monoclonal antibodies, and then use this protocol to validate microfluidic isolation of aptamers targeting patient M-Ig proteins for serum-based M-Ig detection. At the end of the three-year grant period, we would be ready to initiate a clinical study, including longitudinal, real-time monitoring of actual patients with intact immunoglobulin multiple myeloma (IIMM) with increased levels of the IgG1/kappa monoclonal antibody, while in parallel we will expand and generalize our procedure to other classes/subclasses, enabling personalized reagents capable of dramatically improving MRD detection for optimal care for nearly all MM patients.


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: 2022 ( Subtotal = $0 )
2022	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	202 LOW LIBRARY 535 W 116 ST MC 4309,	NEW YORK	NY	10027	NEW YORK	USA	Cancer Detection and Diagnosis Research	000	3	12/3/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	116TH AND BDWY	NEW YORK	NY	10027	NEW YORK	USA	Cancer Detection and Diagnosis Research	000	3	7/16/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $386,051 )
2018	2018	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	116TH AND BDWY	NEW YORK	NY	10027	NEW YORK	USA	Cancer Detection and Diagnosis Research	000	3	9/11/2018	NON-COMPETING CONTINUATION	$386,051
														Subtotal = $386,051

Issue Date FY: 2017 ( Subtotal = $390,115 )
2017	2017	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	116TH AND BDWY	NEW YORK	NY	10027	NEW YORK	USA	Cancer Detection and Diagnosis Research	000	2	7/20/2017	NON-COMPETING CONTINUATION	$390,115
														Subtotal = $390,115

Issue Date FY: 2016 ( Subtotal = $394,518 )
2016	2016	COLUMBIA UNIVERSITY	615 WEST 131ST ST, 4TH FLOOR	NEW YORK	NY	10027	NEW YORK	USA	Cancer Detection and Diagnosis Research	000	1	9/7/2016	NEW	$394,518
														Subtotal = $394,518

Grand Total All Awards = $1,170,684

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Validating Rapid Microfluidic Isolation of Personalized Aptamers for Monitoring Minimal Residual Disease in Multiple Myeloma

Award Number: R33CA196470

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer