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 (GigaLentiTM) 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.
