This $300,000 federal Project Grant award from the National Institutes of Health (NIH) under the Trans-NIH Research Support program (CFDA 93.310) aims to engineer human regulatory T cells (Tregs) with a chimeric antigen receptor (CAR) targeting NTPDase3 on B cells for controlling type 1 diabetes (T1D). The project, led by Sanford Research, will test CAR Tregs with varying antigen binding affinities to optimize their activation, proliferation, and suppressive function against islet-reactive T...
The National Institute of Allergy and Infectious Diseases (NIAID) awarded a $231,131 Project Grant (CFDA 93.855 - Allergy and Infectious Diseases Research) to Duquesne University of the Holy Spirit to develop injectable 3D-clustered human fibroblastic reticular cells (clFRCs) for expanding regulatory T cells (Tregs) to manage allograft transplant rejection. The 2-year project, running from June 2025 to May 2027, aims to optimize the clFRC prototype to generate Tregs in vitro and characterize the...
This $295,924 Project Grant awarded by the National Institute of General Medical Sciences (NIGMS) Biomedical Research and Research Training program (CFDA 93.859) aims to develop and demonstrate a high-yield microfluidic device for the enrichment and capture of CD3+ T cells. This device is intended to improve the manufacturing of autologous and allogenic engineered cell therapies such as CAR-T, which currently have time-consuming and costly production processes. The key objectives are to (1)...
This $693,880 Project Grant award from the National Cancer Institute's Cancer Treatment Research program (CFDA 93.395) supports the development of a novel cancer immunotherapy approach using engineered CD4+ T cells. The goal is to create CD4+ T cells that can target the tumor microenvironment and overcome resistance to current immune checkpoint inhibitor therapies. Key elements include: Identifying key molecules and immune cell targets of the engineered CD4+ T cells in preclinical cancer...
Rattan Life Science Inc. received a $275,000 Project Grant award from the National Science Foundation under the NSF Technology, Innovation, and Partnerships program (CFDA 47.084) to develop a platform for generating induced pluripotent stem cell-derived naïve CD4+ and CD8+ T cells with fidelity, reproducibility and scalability. The platform employs proprietary induced thymic epithelial cells to provide biologically relevant thymic positive selection signals during T cell differentiation,...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 - Allergy and Infectious Diseases Research) provides $196,992 to the University of California, Los Angeles (UCLA) to conduct research on developing regulatory T cells (Tregs) from induced pluripotent stem cells (iPSCs) for potential treatment of autoimmune diseases. The key objectives are to study the role of the transcription factor FOXP3 in Treg development from iPSCs, link exogenous FOXP3...
This Project Grant award from the National Cancer Institute's Cancer Detection and Diagnosis Research program (CFDA 93.394) provides $650,450 to the University of Southern California to develop a novel cancer immunotherapy using genetically engineered CD4+ T cells targeting the CT83 tumor antigen. The research aims to determine the mechanisms by which these engineered T cells eliminate lung cancer cells, produce GMP-grade master cell banks and viral particles, and develop a scalable...
This federal Project Grant award of $207,900 from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) under the CFDA 93.286 "Discovery and Applied Research for Technological Innovations to Improve Human Health" program supports research at The Leland Stanford Junior University (Stanford University) to develop a three-cell synthetic immunotherapy system. The goal is to engineer T cells, natural killer (NK) cells, and macrophages to express chimeric antigen...
This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $399,958 to Mabswitch Inc., a minority-owned small business, to assess the feasibility of regulating the activation, effector functions, and cytokine release of chimeric antigen receptor (CAR) T-cell therapies. The project aims to develop a "switchable affinity CAR" (SAEFCAR) that can be controlled by an exogenously administered ligand, potentially mitigating the toxicity...
This Project Grant award of $194,740 from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), supports research to characterize the development of lung-resident, self-antigen-specific regulatory T cells (Tregs) following acute lung injury. The goal is to understand how these "experienced" Tregs can promote tolerance and prevent future autoimmunity. The principal investigator, Dr. Daniel Shin at...
TOWARD GMP PRODUCTION OF ANTIGEN SPECIFIC REGULATORY T CELLS - ABSTRACT THERE IS AN UNMET NEED FOR MORE SELECTIVE AND SUSTAINABLE THERAPEUTICS TO TREAT A GROWING NUMBER OF IMMUNE- RELATED DISEASES. FOR EXAMPLE, AUTOIMMUNE DISORDERS AFFECT MORE THAN 50 MILLION PATIENTS IN THE UNITED STATES ALONE AND THERE WAS A 3.4% ANNUAL INCREASE IN TYPE 1 DIABETES AMONG EUROPEAN CHILDREN BETWEEN 1989 AND 2013. WHILE CONVENTIONAL TREATMENTS MAY ALLEVIATE SYMPTOMS, THEY ARE OFTEN LESS SPECIFIC AND REQUIRE LONG-TERM MEDICATION. THERE IS A GROWING INTEREST IN DEVELOPING "LIVING DRUGS" WITH REGULATORY T (TREG) CELLS FOR TREATING VARIOUS IMMUNITY-RELATED DISEASES, GIVEN BETTER UNDERSTANDING OF IMMUNOLOGICAL HOMEOSTASIS AND RECENT PROMISING CLINICAL OUTCOMES FROM APPLYING ADOPTIVE CELL THERAPIES. MANY EARLY-PHASE CLINICAL TRIALS WITH TREG CELL PRODUCTS HAVE DEMONSTRATED THE FEASIBILITY AND SAFETY OF THIS APPROACH. STANDARDIZING TREG CELL MANUFACTURING HAS BEEN A SUBSTANTIAL CHALLENGE, INVOLVING CHOICE OF CELL SOURCE, METHODS FOR PURIFYING, ENGINEERING, AND EXPANDING TREG CELLS, PRODUCT SPECIFICATION, AND RELEASE CRITERIA. OVER THE PAST SEVERAL YEARS, WE HAVE BEEN DEVELOPING TARGETED MICROBUBBLE-BASED METHODS FOR STREAMLINING THE MANUFACTURING PROCESSES FOR THERAPEUTIC CELL PRODUCTION, INCLUDING T CELL SELECTION, ACTIVATION, AND ENGINEERING. ONE OF THE MAJOR HURDLES FOR TREG CELL MANUFACTURING IS ISOLATING HIGH PURITY CELLS THAT CAN BE GREATLY EXPANDED AT SCALE FOR CLINICAL THERAPY. TO ISOLATE TREG CELLS IN HIGH PURITY, MULTIPARAMETRIC SORTING USING A SET OF SURFACE MARKERS (E.G. CD4, CD25, CD127) IS NEEDED. THE TWO CURRENT MAJOR TECHNIQUES, FLUORESCENCE-ACTIVATED CELL SORTING (FACS) AND MAGNETIC CELL SORTING (MACS), ALONE CANNOT MEET THE DEMAND FOR ISOLATING LARGE-SCALE GMP GRADE TREG CELLS OF HIGH PURITY. WE HAVE RECENTLY INVENTED AN ITERATIVE, TARGETED MICROBUBBLE-BASED PLATFORM FOR MULTIPLE PARAMETRIC CELL SORTING AT SCALE FROM APHERESIS BLOOD SAMPLES. IN ADDITION, WE HAVE ALSO DEMONSTRATED THAT ANTI-CD3/CD28 CONJUGATED MICROBUBBLES ARE VERY EFFICIENT FOR BEAD-FREE T CELL ACTIVATION AND LONG-TERM EXPANSION. WITH THIS FOUNDATION, WE WILL BUILD AN INNOVATIVE PLATFORM FOR TREG CELL PROCESSING, AND WILL DEMONSTRATE THE FEASIBILITY OF PRODUCING ADEQUATE FUNCTIONAL TREG CELLS OF HIGH PURITY FROM APHERESIS BLOOD SAMPLES IN PHASE I. SUBSEQUENTLY, WE WILL GENERATE ANTIGEN-SPECIFIC CAR (CHIMERIC ANTIGEN RECEPTOR) TREG CELLS THAT MEET CLINICAL SPECIFICATIONS IN PHASE II. ONCE SUCCESSFUL, THIS COULD ACCELERATE THE ADOPTION OF THIS PROMISING THERAPY TO ACCOMPLISH DURABLE RESPONSES OF SUPPRESSING REJECTION FOLLOWING SOLID ORGAN OR HEMATOPOIETIC STEM CELL TRANSPLANTATION, AS WELL AS COMBATING OTHER IMMUNE-RELATED DISORDERS.