Targeting ROR1 with Vls-101: A Promising ADC for Richter's Syndrome

The ROR1 protein is a receptor found on the surface of certain cancer cells but not in normal adult tissues. It is particularly prevalent in specific blood cancers, such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and diffuse large B cell lymphoma (DLBCL). The antibody UC-961 is designed to bind to ROR1, blocking signals that promote cancer cell survival. VLS-101 is a drug that combines UC-961 with a toxin to target and kill cancer cells expressing ROR1.

In a study using patient-derived xenograft models of Richter's Syndrome (RS), a severe form of lymphoma, it was found that ROR1 is expressed in most RS cells. The presence of ROR1 was confirmed through various tests, and its activation led to the activation of survival pathways in RS cells. When RS tumor cells were treated with VLS-101 outside of the body, the drug induced cell death.

Further tests in animal models showed that VLS-101 effectively reduced tumor growth and prolonged survival in RS models that expressed ROR1. Notably, the drug was effective even when ROR1 was not uniformly present in all tumor cells, suggesting a 'bystander effect' where the drug can still impact nearby cells. Importantly, VLS-101 did not cause any observable adverse effects on the animals.

The study concludes that ROR1 is a potential target for RS, and VLS-101 has shown promise in preclinical models. A Phase 1 clinical trial for VLS-101 is currently underway to evaluate its safety and effectiveness in patients with lymphoid cancers.