Specificity of M25 IgG binding to tumor cells and to different members of the alkaline phosphatase family. (A) M25 IgG1 binds specifically to mesothelioma cell lines M28 and VAMT-1 with no binding to control normal human cells (HS27, a normal foreskin fibroblast cell line; HK-2, a normal kidney epithelial cell line; and HS775Li, a normal primary liver cell line). Apparent KD was estimated by curve-fitting (GraphPad). (B) M25 IgG1 binds specifically to ALPPL2 and ALPP, but not ALPI or ALPL. Flow cytometry analysis of M25 IgG1 binding to CHO-K1 cells transiently expressing each of the four members of the human alkaline phosphate family. ALPPL2, placental like-2 alkaline phosphatase; ALPP, placental alkaline phosphatase; ALPI, intestinal alkaline phosphatase; ALPL, tissue-nonspecific alkaline phosphatase. (C) Upper panel: Binding region determination using hybrid ALPI/ALPP fusion constructs. Sequence information is shown in Supplemental Figure 2S. Lower panel: flow cytometry analysis of binding to HEK293A cells expressing hybrid constructs. Red, binding to HEK293A cells expressing full-length ALPP. Grey, binding to HEK293A cells expressing full-length ALPI. Orange, binding to HEK293A cells expressing ALPI/ALPP hybrid_1. Blue, binding to HEK293A cells expressing ALPI/ALPP hybrid_2. (D) M25 IgG1 IHC staining of FDA standard panel of human frozen normal tissues. Other than placenta trophoblasts, none of the normal tissues studied showed positive staining. Scale bar: 50 μm. Enlarged windows are close-up views; scale bar (blue): 30 μm.