Publications by authors named "Jake Reder"
Inflammatory responses associated with ischemia/reperfusion injury (IRI) play a central role in alloimmunity and transplant outcomes. A key event driving these inflammatory responses is the burst of reactive oxygen species (ROS), with hydrogen peroxide (H O ) as the most abundant form that occurs as a result of surgical implantation of the donor organ. Here, we used a syngeneic rat renal transplant and IRI model to evaluate the therapeutic properties of APP-103, a polyoxalate-based copolymer molecule containing vanillyl alcohol (VA) that exhibits high sensitivity and specificity toward the production of H O .
View Article and Find Full Text PDFNKG2D ligands are widely expressed in solid and hematologic malignancies but absent or poorly expressed on healthy tissues. We conducted a phase I dose-escalation study to evaluate the safety and feasibility of a single infusion of NKG2D-chimeric antigen receptor (CAR) T cells, without lymphodepleting conditioning in subjects with acute myeloid leukemia/myelodysplastic syndrome or relapsed/refractory multiple myeloma. Autologous T cells were transfected with a γ-retroviral vector encoding a CAR fusing human NKG2D with the CD3ζ signaling domain.
View Article and Find Full Text PDFBackground Aims: Adoptive cell therapy employing natural killer group 2D (NKG2D) chimeric antigen receptor (CAR)-modified T cells has demonstrated preclinical efficacy in several model systems, including hematological and solid tumors. We present comprehensive data on manufacturing development and clinical production of autologous NKG2D CAR T cells for treatment of acute myeloid leukemia and multiple myeloma (ClinicalTrials.gov Identifier: NCT02203825).
View Article and Find Full Text PDFArticle Synopsis
- CAR T cell therapy using chimeric antigen receptors (CARs) shows promise in eliminating tumors but can cause severe toxicity due to targeting normal cells.
- Modified NKG2D CAR T cells are effective against various tumors, operating through direct cell killing and cytokine release; however, their ligands can unintentionally affect non-tumor cells.
- High doses of activated NKG2D CAR T cells can lead to acute toxicity akin to cytokine release syndrome, primarily driven by perforin and GM-CSF, with host immune cells also playing a significant role in this adverse reaction.