Research investigates the effect of lymphodepletion with anti-CD45 RIT on immune cell types.
Targeted lymphodepletion with CD45-directed radioimmunotherapy could be a safer and more effective alternative to targeting and depleting immune cells, as compared to comparatively non-specific chemotherapy-derived lymphodepletion. Lymphodepletion is recognized as a crucial step in the development of a favorable immune homeostatic environment in patients prior to adoptive cell therapy (ACT) or CAR-T, using chemotherapy such as fludarabine and cyclophosphamide (flu/cy). Targeted CD45-directed radioimmunotherapy (RIT) lymphodepletion could be a safer and more efficient alternative to targeting and depleting immune cells, including those that are immune suppressor cells and those involved in CRS. Since CD45 is overexpressed in most forms of leukemia and lymphoma, it can also minimize tumor burden. The CD45 antigen is present on all nucleated immune cells of mature lymphoid and myeloid lines, with increased expression. In a Phase III clinical trial, Anti-CD45 RIT, 131I -apamistamab (BC8) is a myeloablative targeted conditioning regimen prior to allogeneic stem cell transplantation in patients with active relapsed/refractory AML. Patient findings showed that low non-myeloablative doses of 131I-apamistamab were able to safely induce transient lymphopenia during dosimetry testing; low-dose anti-CD45 RIT could therefore be a promising targeted modality for successful pre-ACT lymphodepleting. These findings show that targeted CD45 RIT lymphodepletion can be done in a safe and efficient way to promote the progression of a single, low-dose, outpatient regimen (Iomab-ACT) to clinical testing that can effectively replace flu/cy conditioning prior to CAR-T.
Journal of Clinical chemistry and Laboratory Medicine