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Principal Investigator: David Scott Johnson
Organization: GIGAMUNE, INC.
Fiscal Year: 2023
Award: $300,000
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <21+ years old><Activated Lymphocyte><Adoptive Cell Transfers><Adrenal Cortex Hormones><Adult><Adult Human><American><Antibody Fragments><Antigens><Autoimmune Status><Autoimmunity><Autologous><Automobile Driving><Biotech><Biotechnology><CAR T cells><CAR modified T cells><CAR-T><CAR-Ts><CD152><CD152 Antigen><CD152 Gene><CD19><CD19 gene><CD25><CD3><CD3 Antigens><CD3 Complex><CD3 molecule><CD8><CD8B><CD8B1><CD8B1 gene><CTLA 4><CTLA-4 Gene><CTLA4><CTLA4 gene><CTLA4-TM><Cancers><Cell Body><Cell Therapy><Cell surface><Cells><Clinic><Clinical><Corticoids><Corticosteroids><Cytotoxic T-Lymphocyte Protein 4><Cytotoxic T-Lymphocyte-Associated Antigen 4><Cytotoxic T-Lymphocyte-Associated Protein 4><Cytotoxic T-Lymphocyte-Associated Serine Esterase-4><DNA Therapy><Doctor of Philosophy><Economics><Engineering><Eragrostis><FOXP3><FOXP3 gene><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Forkhead Box P3><Gall Bladder><Gallbladder><Gallbladder / Biliar><Gallbladder/Biliary system><Gene Delivery><Gene Transfer Clinical><Genes><Genetic Intervention><Goals><Grant><HSV><Hepatic Cells><Hepatic Parenchymal Cell><Hepatic Transplantation><Hepatocyte><Herpes Simplex Virus><Herpes labialis Virus><IL2R><IL2RA><IL2RA gene><Immune><Immunes><Immunoglobulin Fragments><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><In Vitro><Incidence><Infection><Investigation><JM2><Jobs><LYT3><Lead><Lentivirinae><Lentivirus><Liver><Liver Cells><Liver Grafting><Liver Transplant><Lymphoproliferative Disorders><MHC Receptor><Major Histocompatibility Complex Receptor><Malignant Neoplasms><Malignant Tumor><Methods><Nature><OKT3 antigen><Occupations><Paper><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pb element><Ph.D.><PhD><Phase><Phenotype><Professional Positions><Publishing><Receptor Cell><Regulatory T-Lymphocyte><SBIR><SCURFIN><Safety><Simplexvirus><Small Business Innovation Research><Small Business Innovation Research Grant><Specificity><T cell based therapeutics><T cell based therapy><T cell directed therapies><T cell targeted therapeutics><T cell therapy><T cells for CAR><T-Cell Antigen Receptors><T-Cell Receptor><T-Cells><T-Lymphocyte><T3 Antigens><T3 Complex><T3 molecule><TCGFR><Teff><Teff cell><Testing><TfR2 gene product><Toxic effect><Toxicities><Transferrin Receptor Protein 2><Translating><Transplantation><Transplantation Tolerance><Treg><Tropism><Work><adoptive T cell transfer><adoptive T-cell therapy><adoptive cell therapy><adoptive cellular therapy><adulthood><cell mediated therapies><cell-based therapeutic><cell-based therapy><cellular therapeutic><cellular therapy><chimeric antigen T cell receptor><chimeric antigen receptor><chimeric antigen receptor (CAR) T cells><chimeric antigen receptor T cells><chimeric antigen receptor fusion protein T-cells><chimeric antigen receptor modified T cells><clinical efficacy><clinical investigation><compare cost><constitutive expression><constitutive gene expression><cost><cost comparison><cytotoxic T-lymphocyte antigen 4><driving><economic><effector T cell><engineered T cells><fabrication cost><flow cytophotometry><gene repair therapy><gene therapy><gene-based therapy><genetic therapy><genomic therapy><heavy metal Pb><heavy metal lead><hepatic body system><hepatic organ system><immune suppression><immune suppressive activity><immune suppressive function><immunogen><immunosuppressive activity><immunosuppressive function><immunosuppressive response><improved><in vitro Assay><in vitro Model><in vivo><lipid based nanoparticle><lipid nanoparticle><liver transplantation><lymphoproliferative disease><malignancy><manufacture><manufacturing cost><neoplasm/cancer><next generation><novel><patient oriented outcomes><pre-clinical><preclinical><promoter><promotor><receptor expression><regulatory T-cells><therapeutic T-cell platform><thymus derived lymphocyte><transferrin receptor 2><translational opportunities><translational potential><transplant>