In a phase Ia clinical trial, immune cells called Tregs, which can inhibit anticancer immune responses, were efficiently eliminated from the blood of patients with lung or oesophageal cancer by treatment with the investigational therapeutic antibody KW-0761.

Tregs, which are characterised by expression of the proteins FoxP3 and CD4, have several important roles in the immune system, one of which is to prevent the immune system from attacking the body and causing autoimmune diseases.

However, they also suppress the immune response against cancer, Ueda explained, leading to the hypothesis that depleting Tregs in patients with cancer may augment the natural anticancer immune response.

Ryuzo Ueda, professor in the Department of Tumor Immunology at Aichi Medical College in Nagoya, Japan, and Eiichi Nakayama, a professor at Kawasaki University of Medical Welfare in Kurashiki, Japan, enrolled seven patients with non–small cell lung cancer and three patients with esophageal cancer in the phase Ia clinical trial.

Patients were assigned to receive either 0.1, 0.5, or 1.0 mg of KW-0761 per kg of body weight weekly for eight weeks and then monthly until disease progression.

Blood samples were obtained before the first treatment and then every four weeks, and then analysed by flow cytometry to determine numbers of different immune cells.

Ueda explained that the researchers used the CCR4-targeted antibody KW-0761 to deplete Tregs because activated FoxP3 CD4 Tregs that accumulate in tumour tissue have been shown to express CCR4 molecules on their surface.

The researchers found that the number of FoxP3 CD4 Tregs in the blood of all patients was dramatically reduced following treatment with KW-0761.

Four patients had stable disease, as assessed by RECIST 1.1 criteria.

There were no dose-limiting toxicities and most adverse events were grade 1 or grade 2, with skin-related adverse events occurring most frequently.

Source: AACR