R43AI179244

In vivo gene delivery to regulatory T cells to drastically reduce the cost of regulatory T cell therapy - Project Summary

Project Title: In vivo gene delivery to regulatory T cells to drastically reduce the cost of regulatory T cell therapy
Organization: GIGAMUNE Inc.
PI: David Johnson, Ph.D.

Over 9,000 patients will receive liver transplants this year, and about 75% of those patients will survive at least 5 years. Long-term immune suppression is required for nearly all patients, but most immune suppressants (e.g., corticosteroids) are systemic rather than targeted. Immune suppressants lead to long-term toxicities such as malignancy (5% incidence), lymphoproliferative disorder (3% incidence), and infections.

About 50% of patients never tolerate the transplant to the point where immune suppressants can be removed. Adoptive cell therapies wherein chimeric antigen receptors (CARs) or T cell receptors (TCRs) are engineered into autologous T cells ex vivo have shown strong clinical efficacy and safety. Regulatory T cells engineered with CARs ("CAR Tregs") are a relatively new concept wherein CARs are used to direct antigen-specific immune suppression. CAR-Tregs are under preclinical and clinical investigation for indications such as transplant and autoimmunity, with the goal of inducing long-term tolerance without toxicities.

However, the cost of manufacturing cell therapies is hundreds of thousands of dollars per patient, driving total per-patient costs to up to $1 million per patient. Recent pioneering work used lipid nanoparticles (LNPs) and lentivirus (LVs) to deliver CARs to T cells in vivo, eliminating the need for manufacture of engineered cells ex vivo. GIGAMUNE has developed a novel next-generation lentivirus platform (GIGALENTI™) for in vivo delivery of CARs and TCRs specifically to T cells in vivo.

The specific aim of this Phase I SBIR project is to use in vitro models to assess the translational potential of chimeric antigen receptor gene delivery to regulatory T cells for liver transplant tolerance, at drastically reduced cost compared to conventional cell therapy.

Gigamune

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

California United States

State-Wide

PHS 2022-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed) (PA-22-176)

Amendment Since initial award the End Date has been extended from 03/31/24 to 03/31/25.