R01FD008168
Project Grant
Overview
Grant Description
CD5-deleted chimeric antigen receptor cells (SENZA5 CART5) to enhance immunotherapy against T cell non-Hodgkin lymphoma (NHL): A first-in-human phase I clinical trial - Project summary.
The long-term goal of this research is to change the prognosis of relapsed or refractory (R/R) T-cell non-Hodgkin lymphoma (T-NHL) using next-generation chimeric antigen receptor T-cell (CART) immunotherapy.
CART therapy has led to remarkable clinical outcomes in B-cell malignancies, but the needle has not moved for most other cancers.
Relapsed or refractory T-NHL are considered mostly incurable with available therapies and present a particular challenge for antigen-specific T-cell immunotherapy since normal and malignant T cells largely express the same surface antigens.
Our group developed a novel approach to circumvent CART fratricide by deleting the pan T-cell antigen CD5 in T cells that are transduced to express an anti-CD5 CAR.
Of note, our work demonstrated that the deletion of CD5 also enhances T-cell effector function by enhancing CAR signaling.
The present project seeks to test this discovery in a first-in-human clinical trial to evaluate the feasibility, toxicity, and efficacy of CD5 deleted anti-CD5 chimeric antigen receptor CART for T-NHL.
The central hypothesis of this grant is that CD5 deleted anti-CD5 CAR T cell immunotherapy is safe and can lead to potent and long-term clinical responses against T-cell lymphomas.
Moreover, this research will explore whether the CD5 KO untransduced (CAR-negative) T cells from the CD5 KO CART5 product can provide short-term T-cell immunity in case of CART5 toxicity against the normal T cells that express CD5.
The feasibility of this proposal is underpinned by our preliminary results and our institution’s extensive expertise in translating CART therapies.
A dedicated study team was formed with experts with complementary expertise, including the proposal’s principal investigator (Dr. Barta, clinical lead), co-PI (Dr. Ruella, correlative lead), biostatistician (Dr. Hwang), clinical research staff, and laboratory personnel to ensure the timely success of this proposal.
Financial support has been secured from Vittoria Biotherapeutics, Inc, who serves as trial sponsor.
The central hypothesis will be tested by pursuing two specific aims.
In Aim #1, the phase I clinical trial will be performed to evaluate feasibility, toxicity, and efficacy of autologous CD5-deleted anti-CD5 CAR T-cells for R/R non-leukemic T-NHL.
The trial will utilize a Bayesian optimal interval design to establish the recommended phase II dose.
In Aim #2, two working hypotheses will be tested using clinical samples obtained from Aim #1: I. CD5-deleted CART5 can potently expand and infiltrate tumors; and II. CD5-deleted untransduced cells presented in the product can persist in the blood, limiting T-cell aplasia.
Several laboratory techniques will be used for the correlative studies, including flow cytometry, single-cell transcriptomics, cytokine profile, and digital spatial profiling to study the T-cell dynamics and function in the blood and tumors.
The proposed research is highly relevant to public health because patients with R/R T-NHL have no available cures with standard non-cellular therapies.
This study will significantly impact the field of cancer immunotherapies by developing a novel potent anti-T-cell lymphoma immunotherapy and such address an unmet need in a rare disease.
The long-term goal of this research is to change the prognosis of relapsed or refractory (R/R) T-cell non-Hodgkin lymphoma (T-NHL) using next-generation chimeric antigen receptor T-cell (CART) immunotherapy.
CART therapy has led to remarkable clinical outcomes in B-cell malignancies, but the needle has not moved for most other cancers.
Relapsed or refractory T-NHL are considered mostly incurable with available therapies and present a particular challenge for antigen-specific T-cell immunotherapy since normal and malignant T cells largely express the same surface antigens.
Our group developed a novel approach to circumvent CART fratricide by deleting the pan T-cell antigen CD5 in T cells that are transduced to express an anti-CD5 CAR.
Of note, our work demonstrated that the deletion of CD5 also enhances T-cell effector function by enhancing CAR signaling.
The present project seeks to test this discovery in a first-in-human clinical trial to evaluate the feasibility, toxicity, and efficacy of CD5 deleted anti-CD5 chimeric antigen receptor CART for T-NHL.
The central hypothesis of this grant is that CD5 deleted anti-CD5 CAR T cell immunotherapy is safe and can lead to potent and long-term clinical responses against T-cell lymphomas.
Moreover, this research will explore whether the CD5 KO untransduced (CAR-negative) T cells from the CD5 KO CART5 product can provide short-term T-cell immunity in case of CART5 toxicity against the normal T cells that express CD5.
The feasibility of this proposal is underpinned by our preliminary results and our institution’s extensive expertise in translating CART therapies.
A dedicated study team was formed with experts with complementary expertise, including the proposal’s principal investigator (Dr. Barta, clinical lead), co-PI (Dr. Ruella, correlative lead), biostatistician (Dr. Hwang), clinical research staff, and laboratory personnel to ensure the timely success of this proposal.
Financial support has been secured from Vittoria Biotherapeutics, Inc, who serves as trial sponsor.
The central hypothesis will be tested by pursuing two specific aims.
In Aim #1, the phase I clinical trial will be performed to evaluate feasibility, toxicity, and efficacy of autologous CD5-deleted anti-CD5 CAR T-cells for R/R non-leukemic T-NHL.
The trial will utilize a Bayesian optimal interval design to establish the recommended phase II dose.
In Aim #2, two working hypotheses will be tested using clinical samples obtained from Aim #1: I. CD5-deleted CART5 can potently expand and infiltrate tumors; and II. CD5-deleted untransduced cells presented in the product can persist in the blood, limiting T-cell aplasia.
Several laboratory techniques will be used for the correlative studies, including flow cytometry, single-cell transcriptomics, cytokine profile, and digital spatial profiling to study the T-cell dynamics and function in the blood and tumors.
The proposed research is highly relevant to public health because patients with R/R T-NHL have no available cures with standard non-cellular therapies.
This study will significantly impact the field of cancer immunotherapies by developing a novel potent anti-T-cell lymphoma immunotherapy and such address an unmet need in a rare disease.
Funding Goals
TO ASSIST INSTITUTIONS AND ORGANIZATIONS, TO ESTABLISH, EXPAND, AND IMPROVE RESEARCH, DEMONSTRATION, EDUCATION AND INFORMATION DISSEMINATION ACTIVITIES, ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS), BIOLOGICS, BLOOD AND BLOOD PRODUCTS, THERAPEUTICS, VACCINES AND ALLERGENIC PROJECTS, DRUG HAZARDS, HUMAN AND VETERINARY DRUGS, CLINICAL TRIALS ON DRUGS AND DEVICES FOR ORPHAN PRODUCTS DEVELOPMENT, NUTRITION, SANITATION AND MICROBIOLOGICAL HAZARDS, MEDICAL DEVICES AND DIAGNOSTIC PRODUCTS, RADIATION EMITTING DEVICES AND MATERIALS, FOOD SAFETY AND FOOD ADDITIVES. THESE PROGRAMS ARE SUPPORTED DIRECTLY OR INDIRECTLY BY THE FOLLOWING CENTERS AND OFFICES: CENTER FOR BIOLOGICS EVALUATION AND RESEARCH (CBER), CENTER FOR DRUG EVALUATION AND RESEARCH (CDER), CENTER FOR DEVICES AND RADIOLOGICAL HEALTH (CDRH), CENTER FOR VETERINARY MEDICINE (CVM), CENTER FOR FOOD SAFETY AND APPLIED NUTRITION (CFSAN), NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH (NCTR), THE OFFICE OF ORPHAN PRODUCTS DEVELOPMENT (OPD), THE CENTER FOR TOBACCO PRODUCTS (CTP), AND OFFICE OF REGULATORY AFFAIRS (ORA), AND THE OFFICE OF THE COMMISSIONER (OC). SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAMS: TO STIMULATE TECHNOLOGICAL INNOVATION, TO ENCOURAGE THE ROLE OF SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION BY MINORITY AND DISADVANTAGED PERSONS IN TECHNOLOGICAL INNOVATION. FUNDING SUPPORT FOR SCIENTIFIC CONFERENCES THAT ARE RELEVANT TO THE FDA SCIENTIFIC MISSION AND PUBLIC HEALTH ARE ALSO AVAILABLE.
Grant Program (CFDA)
Awarding Agency
Funding Agency
Place of Performance
Pennsylvania
United States
Geographic Scope
State-Wide
Trustees Of The University Of Pennsylvania was awarded
SENZA5 CART5 for R/R T-NHL: Phase I Trial
Project Grant R01FD008168
worth $3,421,591
from the FDA Office of the Commissioner in September 2025 with work to be completed primarily in Pennsylvania United States.
The grant
has a duration of 4 years and
was awarded through assistance program 93.103 Food and Drug Administration Research.
The Project Grant was awarded through grant opportunity Clinical Studies of Orphan Products Addressing Unmet Needs of Rare Diseases (R01) Clinical Trials Required.
Status
(Ongoing)
Last Modified 11/26/25
Period of Performance
9/30/25
Start Date
8/31/29
End Date
Funding Split
$3.4M
Federal Obligation
$0.0
Non-Federal Obligation
$3.4M
Total Obligated
Activity Timeline
Additional Detail
Award ID FAIN
R01FD008168
SAI Number
R01FD008168-3114083975
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Private Institution Of Higher Education
Awarding Office
75FDA1 FDA Office of Acquisitions and Grants Services
Funding Office
75DA00 FDA OFFICE OF THE COMMISSIONER
Awardee UEI
GM1XX56LEP58
Awardee CAGE
7G665
Performance District
PA-90
Senators
Robert Casey
John Fetterman
John Fetterman
Modified: 11/26/25