IN8bio, Inc. announced a publication in Frontiers in Immunology that reviews IN8bio?s novel approach for solid tumors, such as glioblastoma (GBM), an aggressive form of brain cancer. Cellular therapies, particularly chimeric antigen receptor T cell therapies (CAR-T), have shown promise in hematologic malignancies but have faced significant challenges when applied to solid tumors like GBM. These obstacles include rapid tumor growth, antigen heterogeneity, and limited response to current therapies. The publication, titled: ?Adoptive cell therapy for high grade gliomas using simultaneous temozolomide and intracranial mgmt-modified ?d t cells following standard post-resection chemotherapy and radiotherapy: current strategy and future directions,? explains the mechanism of action behind IN8bio?s novel therapeutic approach called DeltEx Drug Resistance Immunotherapy (DRI) and the current strategy and future directions for this treatment. The INB-200 and INB-400 studies by IN8bio addresses the challenges towards targeting solid tumors by harnessing the innate immune functions of gamma-delta T cells. GBM cells constitutively express stress-associated NKG2D ligands (NKG2DL), which can be further upregulated through the DNA damage response (DDR) pathway triggered by alkylating agents like temozolomide (TMZ).
The current standard of care for newly diagnosed GBM typically involves primary tumor resection followed by six weeks of chemoradiation therapy, succeeded by six cycles of monthly maintenance therapy with TMZ. This regimen typically yields a median progression-free survival (PFS) of 6 to 7 months and an overall survival (OS) ranging from 14 to 16 months. IN8bio?s Phase 1 trial (INB-200) assessing the safety and efficacy of intracranial infusions of autologously derived DeltEx DRI gamma-delta T cells in addition to standard-of-care maintenance therapy suggests that the therapy is manageable with a possible improvement in PFS. In the Phase 1 study, cells from the patient are isolated, expanded and modified prior to being delivered intracranially to the tumor cavity every month in combination with maintenance TMZ. The trial assesses three different dosing regimens from a single dose delivered on cycle 1, day 1 in Cohort 1, to three doses delivered on day 1 of cycles 1-3 in Cohort 2, to six doses delivered on day 1 of cycles 1-6 in Cohort 3. All patients receive 1x107 cells per dose. The trial aims to improve PFS by targeting residual cancer cells. Of the eight patients who have completed scheduled dosing, all have exceeded the median PFS expected with standard-of-care therapy alone. IN8bio is also conducting a Phase 2 clinical trial of a genetically modified autologous gamma-delta T cell therapy (INB-400) targeting newly diagnosed GBM. The study will assess the safety, efficacy and tolerability of genetically modified DeltEx DRI cells at leading medical centers across the United States.