Evaluating Cd83 Expression On Organ-Specific Normal Tissues To Anticipate Potential Toxicity Of Novel Human Cd83-Targeted Chimeric Antigen Receptor (Car) T-Cell

Context and Objective CD83 is expressed on activated CD4+ T-cells, dendritic cells, and acute myeloid leukemia (AML), but its expression level on organ-specific normal tissue is not well investigated. A novel human CD83-targeted CAR T-cell has been developed and shown in preclinical work to treat and prevent graft-versus-host disease (GVHD) and confer graft-versus-leukemia (GVL) activity against AML. The purpose of this study is to evaluate CD83 expression in a panel of normal tissue samples to better characterize CD83 expression. Design and Patients An IRB-approved pilot study utilized specimens collected and maintained by Moffitt after informed consent. Thirty samples of representative normal tissues were utilized, with 3 cores taken from each sample, to construct a tissue microarray (TMA). A second TMA was obtained through the Cooperative Human Tissue Network. CD83 expression was assessed by immunohistochemistry (IHC) after antibody validation. IHC expression was scored by hematopathologists, and immunoreactive scores (IRS) were calculated (product of staining intensity and nominal variable denoting expression percentage). IRS scores of 0–1, 2–3, 4–8, and 9–12 correspond to negative, mild, moderate, and strong expression, respectively. Results TMA constructs included 9 normal tissue types with 6–9 cores each and 51 tissue types with 3 cores each in two separate blocks. Strong expression was seen in plasma cells in lymph nodes and tonsils, pancreas, and parathyroid tissue. Moderate expression was seen in lymph nodes, spleen, tonsil, thymus, lung, mesothelium, kidney, liver, thyroid, bladder, cartilage, cerebral cortex, small bowel, stomach, placenta/amniotic membrane, and endocervix. Mild expression was seen in bone marrow, breast, skin, parotid gland, epididymis/seminal vesicle, esophagus, large bowel, anus, uterus, ovary/fallopian tube, synovium, stomach, gallbladder, aorta, and breast. There was no expression in myocardium, adrenal gland, brain white matter, peripheral nerves, smooth muscle, prostate, or ovarian primary oocyte. Conclusions The present study better characterizes CD83 expression on organ-specific normal tissue. Moderate expression was seen in lymphoid tissue. Further work is needed to determine the impact of CD83-targeted therapy on normal tissue expressing CD83. This data will be used in the development of future clinical trials of novel human CD83-targeted therapies with promising preclinical data.