Targeted photodynamic therapy of cancer using a novel gallium (III) tris (ethoxycarbonyl) corrole conjugated‐mAb directed against cancer/testis antigens 83

Abstract

Photodynamic therapy (PDT) is a noninvasive, highly selective approach to the treatment of tumors. However, its therapeutic effect is limited by long‐lasting skin phototoxicity. Therefore, to compromise this shortcoming, it is preferable to deliver photosensitizers selectively to tumor cells with the aid of antibodies specific against tumor‐associated antigens. Cancer/testis antigens 83 (CT83), also called KK‐LC‐1 or CXorf61, recognized by cytotoxic T lymphocytes (CTL), has become a promising target for immunotherapy. Herein, we developed and characterized a novel mouse CT83 mAb 7G4 with a high affinity with Gallium (III) 5, 10, 15‐tris (ethoxycarbonyl) corrole (1‐Ga), a new and promising photosensitizer in PDT. The enzyme‐linked immunosorbent assay (ELISA), flow cytometry and cytotoxicity activity assays revealed that 7G4‐1‐Ga was able to recognize human CT83 with high specificity. Furthermore, 7G4‐1‐Ga showed greater cytotoxicity to CT83‐expressing human cancer cells in vitro than 1‐Ga. These results suggest that the antibody‐conjugated photosensitizer between anti‐CT83 mAb and 1‐Ga may have a good application in PDT, where the destruction of CT83‐expressing tumor is required.

Mesenchymal stem/stromal cells-derived IL-6 promotes nasopharyngeal carcinoma growth and resistance to cisplatin via upregulating CD73 expression

“…As our previously reported [49,50], the tumor tissue were fixed in formalin, embedded in paraffin, sectioned and then heat-immobilized, quenched the endogenous peroxidase activity and retrieved antigenic epitopes. For immunostaining, primary antibodies against IL-6 (sc-28343, Santa Cruz), CD73 (PA5-29750, Thermo-Fisher), gp80 (IL-6Rα, sc-373708, Santa Cruz), gp130 (sc-655, Santa Cruz), p-STAT3 (sc-8001-R, Santa Cruz), SOX-2 (66411-1-Ig, Proteintech), MMP-9 (sc-393859, Santa Cruz), Ki-67 (27309-1-AP, Proteintech), Vimentin (sc-373717, Santa Cruz) and α-SMA (55135-1-AP, Proteintech) were incubated for 30 min at room temperature, followed by HRP-conjugated secondary detection antibody and diaminobenzidine (DAB).…”

“…Nuclear/cytoplasmic fractions were separated by using Cell Fractionation Kit (Cell Signaling Technology, USA) according to the manufacturer's instructions, and the whole cell lysates were extracted using RIPA Buffer (Cell Signaling Technology). Western blot was performed according to a standard method as described previously [49]. Protein bands were visualized using ECL reagents (Pierce, USA).…”

CAR T-Cell Cancer Therapy Targeting Surface Cancer/Testis Antigens

“…These results, and the fact that PRAME is overexpressed in many malignancies, indicate that PRAME is a promising target for CAR T-cell therapy ( 45 , 46 ). Other CT antigens with a proposed surface localization include CT83, SP17, SLCO6A1, and PLAC1 ( 47 – 50 ). SP17 is overexpressed in multiple cancer types ( 48 , 51 – 56 ), and expression is upregulated by DNMTis ( 57 ).…”

Hypomethylation‐mediated activation of cancer/testis antigen KK‐LC‐1 facilitates hepatocellular carcinoma progression through activating the Notch1/Hes1 signalling

“…Correlated with Helicobacter pylori infection, 7 KK-LC-1 can be frequently detected even in early stage of gastric cancer 8 and at the pre-cancerous condition of the stomach. 10 However, the biological functions and underlying mechanisms of KK-LC-1 in human cancers remain obscure. A recent study has implicated the utility of KK-LC-1 as a target for photodynamic therapy in malignancies.…”