Simultaneous administration of MGMT-modified gamma-delta T cells with temozolomide (TMZ) demonstrated a significant survival benefit in several high-grade glioma models
MGMT-modified gamma-delta T cells designed to survive chemotherapy and form the basis of IN8bio’s drug-resistant immunotherapy (DRI) technology
These results, published online in the journal Nature portfolio Scientific Reports (DOI: https://doi.org/10.1038/s41598-021-00536-8), provide important preclinical support for the clinical development of DRI
DRI with a competitor TMZ The dosage 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 using its DeltEx platform, today announced the peer-reviewed publication of preclinical results which provides fundamental support for the use of IRN in newly diagnosed GBM. This work, published in the Nature portfolio review Scientific reports. Concomitant administration of DRI cells and TMZ resulted in a significant improvement in survival results in mice compared to either monotherapy alone in classical high-grade primary gliomas and mesenchymal gliomas.
These studies were carried out by the scientific co-founder and scientific director of IN8bio, Dr. Lawrence Lamb while he was at UAB, in collaboration with researchers at Emory University, and the technology has been exclusively under worldwide license by IN8bio. This unique technology forms the basis of the company’s DeltEx DRI platform, which uses ex vivo Extended and activated gamma-delta T cells that can be engineered to withstand chemotherapy for solid and liquid tumors. This preclinical work provides support for the simultaneous assay of DRI cells with TMZ to shrink tumor, reduce accumulation of immunosuppressive cells, and upregulate innate activation of effector cells through increased NKG2D ligands. This approach is currently being evaluated 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., director scientist, co-founder of IN8bio and responsible author of the paper. “Unfortunately, TMZ causes lymphodepletion, which impairs the ability of the immune system to take advantage of 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 simultaneous administration. We observed that this concomitant combination resulted in a significant improvement in survival compared to monotherapy or sequential therapy and are now evaluating this regimen in clinical trials.
William Ho, CEO and Co-Founder of IN8bio, said: “This approach, which forms the basis of IN8bio’s DeltEx DRI programs, targets a pathway conserved through evolution, the response to damage to DNA (or DDR), which has potential applicability to a wide range of solid tumors for which chemotherapy remains the mainstay of treatment. This potentially includes combining INB-200 with other approaches such as checkpoint inhibitors and other targeted therapies in orthogonal combinations to maximize impact on the tumor. Combined with our expertise in the genetic engineering of these cells ex-vivo, we look forward to continuing to develop our broad portfolio of gamma-delta T cell 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 have unique properties, including the ability to differentiate healthy tissue from diseased tissue. IN8bio’s DeltEx platform uses allogeneic, autologous and genetically engineered 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 main gamma-delta T cell product candidates: INB-200 for the treatment of newly diagnosed glioblastoma and INB-100 for the treatment of leukemia patients undergoing transplant. hematopoietic stem cells. IN8bio also has a large portfolio of preclinical programs focused on the treatment of other types of solid tumors.
For more information about IN8bio and its programs, please visit www.IN8bio.com.
Certain statements contained in this document regarding the Company’s future expectations, plans and prospects, including, without limitation, the Company’s current expectations regarding the advancement of its product candidates through studies. preclinical and clinical trials, and the outlook for these candidates and the underlying technology, constitute forward-looking statements under the Private Securities Litigation Reform Act of 1995. The use of words such as “may”, “could”, “Will”, “should”, “expect”, “plan”, “anticipate”, “believe”, “estimate,” “project”, “intention”, “future”, “potential” or “continue” , the negative of these and other similar expressions are intended to identify such forward-looking statements. Such statements, based on management’s current expectations, inherently involve numerous risks and uncertainties, known and unknown, many of which are beyond the control of the Company. Therefore, actual future results may differ materially from the anticipated results expressed in these statements. The specific risks that could cause actual results to differ materially from the Company’s current expectations include: scientific, regulatory and technical developments; failure to demonstrate safety, tolerability and efficacy; final, quality-controlled verification of data and associated analyzes; the expense and uncertainty of obtaining regulatory approval, including from the United States Food and Drug Administration; and the Company’s dependence on third parties, including licensors and clinical research organizations. Do not place undue reliance on any forward-looking statements included herein, which speak only as of the date hereof and which the Company is under no obligation to update or revise due to any event, circumstance or otherwise, unless required by applicable law. .
Company details :
Kate Rochlin, Ph.D.
+1 646.600.6 GDT (6438)
+ 1 646.378.2927