Concurrent dosing of MGMT-modified gamma-delta T cells with Temozolomide (TMZ) demonstrated a significant survival benefit across multiple models of high-grade glioma
MGMT-modified gamma-delta T cells are engineered to survive chemotherapy and form the basis of IN8bio's Drug Resistant Immunotherapy (DRI) technology
These results, published online in the Nature portfolio journal Scientific Reports (DOI: https://doi.org/10.1038/s41598-021-00536-8), provide significant preclinical support for the clinical development of DRI
DRI with a concurrent TMZ dosing regimen is currently being evaluated in a Phase 1 clinical trial in glioblastoma multiforme (GBM) at the O'Neal Comprehensive Cancer Center at the University of Alabama at Birmingham (UAB)
NEW YORK, Oct. 27, 2021 (GLOBE NEWSWIRE) -- IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company focused on the discovery and development of innovative gamma-delta T cell therapies utilizing its DeltEx platform, today announced the peer-reviewed publication of preclinical results that provides foundational support for the use of DRI in newly diagnosed GBM. This work, published in the Nature portfolio journal Scientific Reports, focused on the use of gamma-delta T cells genetically engineered to be chemotherapy resistant through the addition of an O6-Methylguanine-DNA Methyltransferase (MGMT) transgene, a process termed Drug Resistant Immunotherapy (or DRI). Concurrent dosing of DRI cells with TMZ resulted in a significant improvement in survival outcomes in mice over either monotherapy alone in both classical and mesenchymal primary high-grade gliomas.
These studies were performed by IN8bio's scientific co-founder and Chief Scientific Officer, Dr. Lawrence Lamb while at UAB, in collaboration with researchers at Emory University, and the technology has been exclusively licensed world-wide by IN8bio. This unique technology forms the basis for the company's DeltEx DRI platform, which utilizes ex-vivo expanded, activated gamma-delta T cells that can be engineered to be chemotherapy resistant for both solid and liquid tumors. This preclinical work provides support for the concurrent dosing of DRI cells with TMZ to debulk the tumor, reduce accumulation of immunosuppressive cells and upregulate innate effector cell activation through an increase in NKG2D-ligands. This approach is currently undergoing evaluation in a Phase 1 trial in patients with newly diagnosed GBM at The University of Alabama at Birmingham.
"Chemotherapeutic agents, including TMZ can upregulate stress induced ligands in tumor cells, which can be recognized by gamma-delta T cells," said Lawrence S. Lamb, Ph.D., Chief Scientific Officer, co-founder of IN8bio and the lead author of the paper. "Unfortunately, TMZ is lymphodepleting, hindering the immune system's ability to leverage this state of increased tumor vulnerability. To overcome this, we developed gamma-delta T cells engineered with a gene conferring resistance to alkylating agents such as TMZ, allowing our MGMT-modified cells to remain functional through concurrent administration. We observed that this concomitant combination resulted in a significant improvement in survival over either monotherapy or sequential therapy and we are now evaluating this regimen in clinical trials."
William Ho, Chief Executive Officer and co-founder of IN8bio said, "This approach, which forms the basis for IN8bio's DeltEx DRI programs targets an evolutionarily conserved pathway, the DNA Damage Response (or DDR), that has potential applicability across a broad range of solid tumors for which chemotherapy remains the mainstay of treatment. This includes potentially combining INB-200 with other approaches such as checkpoint inhibitors and other targeted therapies in orthogonal combinations to maximize the tumor impact. Combined with our expertise in genetically engineering these cells ex-vivo, we look forward to continuing to develop our deep pipeline of gamma-delta T cell based therapies for cancer."
IN8bio is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of gamma-delta T cell product candidates for solid and liquid tumors. Gamma-delta T cells are a specialized population of T cells that possess unique properties, including the ability to differentiate between healthy and diseased tissue. IN8bio's DeltEx platform employs allogeneic, autologous and genetically modified approaches to develop cell therapies, designed to effectively identify and eradicate tumor cells.
IN8bio is currently conducting two investigator-initiated Phase 1 clinical trials for its lead gamma-delta T cell product candidates: INB-200 for the treatment of newly diagnosed glioblastoma and INB-100 for the treatment of patients with leukemia undergoing hematopoietic stem cell transplantation. IN8bio also has a broad portfolio of preclinical programs focused on addressing other solid tumor types.
For more information about IN8bio and its programs, please visit www.IN8bio.com.
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