AI Article Synopsis
- Cancer ranks as one of the deadliest diseases globally, with advanced metastatic carcinoma leading in mortality, highlighting the urgent need for new targeted therapies.
- Researchers developed a novel antibody fusion protein, 57103, which effectively targets multiple receptors and exhibited significant anti-cancer effects in vitro by suppressing the growth, migration, and invasion of renal cancer cells.
- In animal studies, 57103 demonstrated the ability to inhibit tumor growth and promote cancer cell death while also improving immune responses, indicating its potential as a treatment for metastatic renal carcinoma or other cancers that overexpress PDL1.
Article Abstract
Cancer is one of the top 10 fatal diseases worldwide, among which advanced metastatic carcinoma has the highest mortality rate. Sunitinib and immune checkpoint blockers are commonly used to treat metastatic renal carcinoma with limited efficacy. Therefore, there is an urgent need to develop novel targeted therapies for metastatic renal cancer. In this study, we designed an antibody fusion protein, 57103, that simultaneously targeted the cluster of differentiation 24 (CD24), interleukin 4 receptor (IL-4R), and integrin receptors αβ and αβ. In vitro assays showed that 57103 significantly suppressed the proliferation, migration, invasion, colony formation, and adhesion abilities of renal cancer cells, resulting in a comprehensive and significant antitumor effect. Furthermore, 57103 inhibited angiogenesis, promoted THP1-derived M0-type macrophage phagocytosis, and enhanced the antibody-dependent cellular cytotoxicity of peripheral blood mononuclear and NK92MI-CD16a cells. In vivo experiments revealed significant inhibition of tumor growth in ACHN cell xenograft nude mice and an MC38-hCD24 tumor-bearing mouse model. Immunohistochemical analysis showed that 57103 decreased the proliferation and induced the apoptosis of renal cancer cells, while inhibiting angiogenesis. The MC38-hPDL1 and MC38-hCD24-hPDL1 tumor-bearing mouse models further offer the possibility of combining 57103 with the PDL1 antagonist atezolizumab. In conclusion, 57103 is a potential candidate drug for the treatment of metastatic renal carcinoma or PDL1-overexpressing cancer.
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| http://dx.doi.org/10.1016/j.biopha.2024.116714 | DOI Listing |
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