Sensitive CAR T cells redefine targetable CD70 expression in solid tumors [ATAC-seq]

CD70 expression in solid tumors is heterogeneous. We demonstrate that cells appearing CD70-negative retain ultra-low levels of CD70 expression. These cells that appear negative by conventional detection methods. Bulk ATAC-seq analysis of FACS-sorted CD70? and CD70? tumor populations revealed differential chromatin accessibility, indicating epigenetic regulation of CD70 expression in both ccRCC and HGSOC models. Overall design: NSG mice (n = 3 per model) were implanted with ccRCC patient-derived xenograft (PDX) lines (K5 and K7) under the renal capsule. Fifteen days post-implantation, tumors were isolated and dissociated for FACS sorting into CD70? and CD70? tumor cell populations. Protein, RNA, and chromatin accessibility (ATAC-seq) were profiled at isolation (day 0 ex vivo) and during culture at day 2 and day 8 ex vivo. An analogous procedure was performed for an ovarian carcinoma (HGSOC) PDX line 32 days post tumor implantation.