Blocking the functional domain of TIP1 by antibodies sensitizes cancer to radiation therapy

Area of Science:

• Oncology
• Molecular Biology
• Immunotherapy

Background:

• Non-small-cell lung cancer (NSCLC) and glioblastoma (GB) are aggressive cancers with poor prognoses, necessitating novel therapeutic targets.
• Tax interacting protein 1 (TIP1) is implicated in cancer progression and is overexpressed and radiation-inducible in NSCLC and GB.

Purpose of the Study:

• To evaluate the therapeutic potential of an anti-TIP1 antibody, alone and in combination with ionizing radiation (XRT), against NSCLC and GB.
• To elucidate the molecular mechanisms underlying the anti-cancer effects of anti-TIP1 antibodies.

Main Methods:

• In vitro studies involved treating NSCLC and GB cells with anti-TIP1 antibodies to assess proliferation, colony formation, endocytosis, and cell death.
• In vivo efficacy was measured using mouse models of NSCLC and GB treated with anti-TIP1 antibodies and/or XRT.
• mRNA sequencing was employed to investigate the molecular pathways affected by anti-TIP1 antibody treatment.

Main Results:

• Targeting TIP1's functional domain induced antibody endocytosis, leading to reduced cancer cell proliferation and increased apoptosis.
• Anti-TIP1 antibodies demonstrated specific, high-affinity binding to cancer cells and synergized with XRT to enhance cytotoxicity in vitro.
• Significant tumor growth reduction was observed in mouse models, accompanied by the downregulation of cancer survival signaling pathways.

Conclusions:

• TIP1 represents a novel therapeutic target for NSCLC and GB.
• Antibodies targeting TIP1's functional domain exhibit potent antitumor activity and enhance radiation therapy efficacy.
• Anti-TIP1 antibodies offer a promising therapeutic strategy, both as monotherapy and in combination with XRT, for treating NSCLC and GB.