R41AI186797
Project Grant
Overview
Grant Description
The development of a GMP EDHFR vector to monitor investigational CAR T cell therapies - Abstract
The development of cell and gene therapies like chimeric antigen receptor (CAR) T cells has necessitated new technologies that can monitor the biodistribution and trafficking pattern of these therapies in human patients.
Imaging is particularly well suited to provide quantitative measurements of such therapies over time.
Vellum Biosciences is a platform imaging company geared to fill this void in available technologies, providing repeatable, robust, and sensitive measures of genetic medicine in situ with clear applications in new drug development, clinical research, and eventually, clinical practice.
Vellum’s technology is based on positron emission tomography (PET) radiotracer derivatives of the synthetic antibiotic trimethoprim (TMP) and engineered expression of its protein target E. coli dihydrofolate reductase (EDHFR).
When EDHFR is expressed via a genetic medicine (e.g., cells harboring lentiviral or adeno-associated viral vectors or therapeutic mRNA), TMP radiotracers can be used to measure the expression of the protein products in any tissue within the body.
Our strategy has been used to monitor the trafficking of CAR T cells targeting several types of tumors in rodents in collaboration with several different research groups at the University of Pennsylvania (UPENN) and a global pharmaceutical company.
In this STTR Phase 1, we propose the development of a GMP-compliant EDHFR viral vector that can be applied in a modular fashion to different cellular therapies to monitor their biodistribution over time.
This “stand-alone” imaging vector dovetails with Vellum and UPENN’s ongoing collaborative STTR Phase I grant focused on optimizing [18F]-FTMP production to provide a commercial supply of the radiotracer (R41EB034141).
In Aim 1, we will evaluate the feasibility of using a stand-alone imaging vector format in vitro, which can then be applied to different cellular therapies in collaboration with the Penn Center for Cellular Immunotherapies (CCI).
In Aim 2, we take the enabling steps to perform quality control measures and functional assessment of the vector both in vitro and in vivo and take the necessary steps to manufacture a GMP-compliant EDHFR lentiviral vector.
This process has been initiated via an established relationship with a CRO to produce the IND-ready DNA plasmids in collaboration with the CCI and with the “line-of-sight” assistance of the Penn Vector Core for the future clinical grade lentivirus.
Taken together, these short-term aims will provide the evidence base needed for the final justification and creation of EDHFR viral vectors that allow monitoring of investigational cell therapies in patients at UPENN.
We envision that our approach will substantially impact our understanding of why a cell therapy product is successful or fails on an individual patient level using non-invasive imaging.
The development of cell and gene therapies like chimeric antigen receptor (CAR) T cells has necessitated new technologies that can monitor the biodistribution and trafficking pattern of these therapies in human patients.
Imaging is particularly well suited to provide quantitative measurements of such therapies over time.
Vellum Biosciences is a platform imaging company geared to fill this void in available technologies, providing repeatable, robust, and sensitive measures of genetic medicine in situ with clear applications in new drug development, clinical research, and eventually, clinical practice.
Vellum’s technology is based on positron emission tomography (PET) radiotracer derivatives of the synthetic antibiotic trimethoprim (TMP) and engineered expression of its protein target E. coli dihydrofolate reductase (EDHFR).
When EDHFR is expressed via a genetic medicine (e.g., cells harboring lentiviral or adeno-associated viral vectors or therapeutic mRNA), TMP radiotracers can be used to measure the expression of the protein products in any tissue within the body.
Our strategy has been used to monitor the trafficking of CAR T cells targeting several types of tumors in rodents in collaboration with several different research groups at the University of Pennsylvania (UPENN) and a global pharmaceutical company.
In this STTR Phase 1, we propose the development of a GMP-compliant EDHFR viral vector that can be applied in a modular fashion to different cellular therapies to monitor their biodistribution over time.
This “stand-alone” imaging vector dovetails with Vellum and UPENN’s ongoing collaborative STTR Phase I grant focused on optimizing [18F]-FTMP production to provide a commercial supply of the radiotracer (R41EB034141).
In Aim 1, we will evaluate the feasibility of using a stand-alone imaging vector format in vitro, which can then be applied to different cellular therapies in collaboration with the Penn Center for Cellular Immunotherapies (CCI).
In Aim 2, we take the enabling steps to perform quality control measures and functional assessment of the vector both in vitro and in vivo and take the necessary steps to manufacture a GMP-compliant EDHFR lentiviral vector.
This process has been initiated via an established relationship with a CRO to produce the IND-ready DNA plasmids in collaboration with the CCI and with the “line-of-sight” assistance of the Penn Vector Core for the future clinical grade lentivirus.
Taken together, these short-term aims will provide the evidence base needed for the final justification and creation of EDHFR viral vectors that allow monitoring of investigational cell therapies in patients at UPENN.
We envision that our approach will substantially impact our understanding of why a cell therapy product is successful or fails on an individual patient level using non-invasive imaging.
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Pennsylvania
United States
Geographic Scope
State-Wide
Vellum Biosciences was awarded
Project Grant R41AI186797
worth $300,000
from the National Institute of Allergy and Infectious Diseases in August 2024 with work to be completed primarily in Pennsylvania United States.
The grant
has a duration of 1 year and
was awarded through assistance program 93.855 Allergy and Infectious Diseases Research.
The Project Grant was awarded through grant opportunity PHS 2023-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed).
SBIR Details
Research Type
STTR Phase I
Title
The development of a GMP eDHFR vector to monitor investigational CAR T cell therapies
Abstract
Abstract The development of cell and gene therapies like Chimeric Antigen Receptor (CAR) T cells has necessitated new technologies that can monitor the biodistribution and trafficking pattern of these therapies in human patients. Imaging is particularly well suited to provide quantitative measurements of such therapies over time. Vellum Biosciences is a platform imaging company geared to fill this void in available technologies, providing repeatable, robust, and sensitive measures of genetic medicine in situ with clear applications in new drug development, clinical research, and eventually, clinical practice. Vellum’s technology is based on positron emission tomography (PET) radiotracer derivatives of the synthetic antibiotic trimethoprim (TMP) and engineered expression of its protein target E. coli dihydrofolate reductase (eDHFR). When eDHFR is expressed via a genetic medicine (e.g., cells harboring lentiviral or adeno-associated viral vectors or therapeutic mRNA), TMP radiotracers can be used to measure the expression of the protein products in any tissue within the body. Our strategy has been used to monitor the trafficking of CAR T cells targeting several types of tumors in rodents in collaboration with several different research groups at the University of Pennsylvania (UPenn) and a global pharmaceutical company. In this STTR phase 1, we propose the development of a GMP-compliant eDHFR viral vector that can be applied in a modular fashion to different cellular therapies to monitor their biodistribution over time. This “stand-alone” imaging vector dovetails with Vellum and UPenn’s on-going collaborative STTR Phase I grant focused on optimizing [18F]-FTMP production to provide a commercial supply of the radiotracer (R41EB034141). In Aim 1, we will evaluate the feasibility of using a stand-alone imaging vector format in vitro, which can then be applied to different cellular therapies in collaboration with the Penn Center for Cellular Immunotherapies (CCI). In Aim 2, we take the enabling steps to perform quality control measures and functional assessment of the vector both in vitro and in vivo and take the necessary steps to manufacture a GMP-compliant eDHFR lentiviral vector. This process has been initiated via an established relationship with a CRO to produce the IND-ready DNA plasmids in collaboration with the CCI and with the “line-of-sight” assistance of the Penn Vector Core for the future clinical grade lentivirus. Taken together, these short-term aims will provide the evidence base needed for the final justification and creation of eDHFR viral vectors that allow monitoring of investigational cell therapies in patients at UPenn. We envision that our approach will substantially impact our understanding of why a cell therapy product is successful or fails on an individual patient level using non-invasive imaging.
Topic Code
NIAID
Solicitation Number
PA23-232
Status
(Complete)
Last Modified 8/20/24
Period of Performance
8/7/24
Start Date
7/31/25
End Date
Funding Split
$300.0K
Federal Obligation
$0.0
Non-Federal Obligation
$300.0K
Total Obligated
Activity Timeline
Additional Detail
Award ID FAIN
R41AI186797
SAI Number
R41AI186797-1458510285
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Small Business
Awarding Office
75NM00 NIH NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Funding Office
75NM00 NIH NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Awardee UEI
EVYDGHYR7LK6
Awardee CAGE
97LB4
Performance District
PA-90
Senators
Robert Casey
John Fetterman
John Fetterman
Modified: 8/20/24