19 August 2019

A combination therapy is being developed that could benefit patients with treatment-resistant acute lymphoblastic leukaemia (ALL), US scientists have reported.

The treatment, developed by Dr Reshmi Parameswaran and colleagues at Case Western Reserve University in Ohio, USA, is based attracting natural killer (NK) cells in the immune system to destroy cancer cells.

New immune therapies have helped improve survival rates for acute lymphoblastic leukaemia. However, there are still patients whose cancer is unresponsive to treatment or suffer from drug-related toxicities or drug resistance.

In the study, the team tested an antibody which rapidly recruits NK cells to attack ALL cells. The antibody binds to a protein on the surface of the ALL cells called B-cell Activating Factor Receptor (BAFF‑R), and acts like a ‘flag’ to attract NK cells.

The therapy was tested on mice with drug-resistant cancer cells donated by human patients. The researchers found that the anti-BAFF-R drug works best when used early in the disease process.

Dr Parameswaran says: “If we started to treat mice with the antibody early during disease development, leukaemia was almost eradicated by this treatment method; however, if treatment was administered late when the tumour had grown and established its own microenvironment, the antibody alone was less effective.”

To combat the tumour’s protective microenvironment, the team added a TGF-beta receptor inhibitor. TGF-beta is normally secreted by cancer cells to block attacks from NK cells.

“There was a clear negative effect of the tumour microenvironment on natural killer cell killing capacity,” Dr Parameswaran explained. “So, we added a TGF-beta receptor inhibitor to our antibody treatment regimen.”

Together, the two drugs increased NK cell activity again ALL cells by up to 35%, say the researchers, who recently published their work in Cancer Immunology Research.

The team hope that their combination therapy “could represent a promising new regimen for late-stage acute lymphoblastic leukaemia, particularly benefitting adults who are unresponsive to existing options”.

Source: Vicioso, Y., Gram, H., Beck, R., Asthana, A., Zhang, K., Wong, D.P., Letterio, J., Parameswaran, R. (2019) “Combination therapy for treating advanced drug-resistant acute lymphoblastic leukemia”, Cancer Immunology Research, available from doi: 10.1158/2326-6066.CIR-19-0058


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