An ROR1 bi-specific T-cell engager provides effective targeting and cytotoxicity against a range of solid tumors

Area of Science:

• Oncology
• Immunotherapy
• Molecular Biology

Background:

• Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a cell surface antigen found on various malignancies and cancer-initiating cells.
• Targeting ROR1 presents a potential therapeutic strategy for cancers with significant unmet needs.

Purpose of the Study:

• To develop and evaluate a humanized bispecific T-cell engager (BiTE) targeting ROR1.
• To assess the efficacy of the ROR1 BiTE in preclinical models of pancreatic and ovarian cancer, and other solid tumors.

Main Methods:

• Development of a humanized ROR1-targeting BiTE.
• In vitro assessment of T-cell-mediated cytotoxicity against ROR1-expressing cancer cell lines.
• In vivo studies using murine models of pancreatic cancer xenografts and ovarian cancer.
• Evaluation of T-cell-mediated killing across diverse solid tumor cell lines.

Main Results:

• The ROR1 BiTE induced potent, antigen-specific T-cell-mediated cytotoxicity against ROR1-expressing pancreatic cancer cells in vitro at low concentrations (0.1 ng/mL).
• In vivo, the ROR1 BiTE prevented pancreatic tumor xenograft engraftment and reduced established tumor size by over 3-fold.
• Significant cytotoxicity was observed in ovarian cancer models (in vitro and in vivo), and T-cell-mediated killing was demonstrated across various solid tumor types.

Conclusions:

• The developed ROR1 BiTE is a promising immunotherapy agent with broad applicability.
• This approach demonstrates significant potential for treating a wide range of malignancies, particularly those with limited therapeutic options.