Preparation of a Growth Hormone Receptor/Prolactin Receptor Bispecific Antibody Antagonist Which Exhibited Anti-Cancer Activity

Abstract

Prolactin receptor (PRLR) and growth hormone receptor (GHR) are closely related to the occurrence and development of breast cancer, and breast cancer cell endogenously express GHR, PRLR and GHR-PRLR heterodimer. In this case, the combined use of PRLR or GHR inhibitors may produce better anti-breast cancer potential than PRLR or GHR inhibitors alone. In this case, it is necessary to develop the dual-function GHR/PRLR antagonists with anti-breast cancer potential. For this, we used hybridoma technology to generate an anti-idiotypic antibody (termed H53). We then used various techniques, including competitive ELISA, competitive receptor binding analysis, and indirect immunofluorescence assay to identify H53, and the results show that H53 behaves as a typical internal image anti-idiotypic antibody (Ab2β). Further experiments indicate that H53 is a dual-function inhibitor, which not only inhibited PRLR-mediated intracellular signaling, but also blocked GHR-mediated intracellular signaling in a dose-dependent manner. Furthermore, H53 could inhibit PRL/GH-driven cancer cell proliferation in vivo and in vitro. This study indicates that H53 exhibits potential biological activity against breast tumors, which implies that internal image anti-idiotypic antibodies may be a useful strategy for the development of PRLR/GHR dual-function antagonists for breast cancer therapy.

Prolactin receptor signaling: A novel target for cancer treatment - Exploring anti-PRLR signaling strategies

“…As PRLR and growth hormone receptor (GHR) are closely involved in the incidence and development of breast cancer (98) which typically express PRLR, GHR, and GHR-PRLR heterodimers (99), the use of a combination PRLR and GHR antagonists may be a better strategy for breast cancer treatment. As such, Chen et al have used a hybridoma technology to design a dual GHR-PRLR targeting antibody called H53 (100). Using competitive ELISA, receptor binding analysis, and immunofluorescence assays, the authors identified that H53 behaved like a typical anti-idiotypic antibody (Ab2b) (100).…”

“…As such, Chen et al have used a hybridoma technology to design a dual GHR-PRLR targeting antibody called H53 (100). Using competitive ELISA, receptor binding analysis, and immunofluorescence assays, the authors identified that H53 behaved like a typical anti-idiotypic antibody (Ab2b) (100). Further testing revealed that H53 treatment (0.05-1 mg/ml) inhibited not only the growth of CHO cells expressing PRLR and GHR but also PRLR-induced JAK2-STAT5 signaling (100).…”

“…Using competitive ELISA, receptor binding analysis, and immunofluorescence assays, the authors identified that H53 behaved like a typical anti-idiotypic antibody (Ab2b) (100). Further testing revealed that H53 treatment (0.05-1 mg/ml) inhibited not only the growth of CHO cells expressing PRLR and GHR but also PRLR-induced JAK2-STAT5 signaling (100). H53 also inhibited the PRL-induced phosphorylation of both STAT3 and STAT5, and AKT at a dose of 5-10 g/ml in T47D and MCF7 breast cancer cell lines, and further attenuated PRLinduced proliferation (100).…”

“…Further testing revealed that H53 treatment (0.05-1 mg/ml) inhibited not only the growth of CHO cells expressing PRLR and GHR but also PRLR-induced JAK2-STAT5 signaling (100). H53 also inhibited the PRL-induced phosphorylation of both STAT3 and STAT5, and AKT at a dose of 5-10 g/ml in T47D and MCF7 breast cancer cell lines, and further attenuated PRLinduced proliferation (100). Moreover, H53 also inhibited clonogenic potential, and migration that was accompanied by decreased expression of PRLR and GHR (100).…”

Hormone supply to the pituitary gland: A comprehensive investigation of female‑related tumors (Review)

“…Chen et al used hybridoma technology to generate an anti-idiotypic antibody named H53. H53 exhibits biological activity against breast cancer, suggesting that an internal image with anti-idiotypic antibodies may be a candidate strategy to develop PRLR/GHR dual-function antagonists for breast cancer therapy (67). PRL has further been shown to promote pancreatic ductal adenocarcinoma, which, notably, can be reversed by antipsychotic diphenylbutylpiperidines (68).…”