New Target Helps Enhance the Anti-Tumor Response of Immunotherapy

Immune-related adverse events from immunotherapy treatment may be overcome by targeting the cytokine interleukin-6 (IL-6) as per a study at The University of Texas MD Anderson Cancer Center, published in Cancer Cell.

Although the combination immunotherapy (with anti-PD-1 and anti-CTLA-4 agents) has revolutionized treatment for multiple cancer types, it also has high toxicity rates, and poor outcomes towards treatment continuation and quality of life.

‘Side effects/toxicity of immunotherapy may be relieved by targeting interleukin-6 (IL-6) and immune checkpoint blockade while preserving anti-tumor immune response.’

The study team used several preclinical models to evaluate the effect of an IL-6 blockade on autoimmunity and response to anti-CTLA-4 therapy.

"We need to overcome immune toxicity, first and foremost, to support patients and reduce their symptom burden. Secondly, we know that there are multiple, non-overlapping mechanisms of resistance in the tumor microenvironment. In order to build an effective multi-agent immunotherapy regimen, we have to overcome the barrier of immune-related toxicity so that patients can continue receiving the optimum treatment," says senior author Adi Diab, from The University of Texas MD Anderson Cancer Center.

Novel Target to Enhance Immunotherapy

The present findings thereby establish a proof of concept for combining immune checkpoint blockade with cytokine blockers to selectively inhibit inflammatory autoimmune responses.

The findings were further validated through a retrospective analysis of 31 melanoma patients who were treated efficiently with immune checkpoint blockade.

"Cytokine blockers have been well established to block autoimmunity. The novelty of this study is bringing cytokine targeting to tumor immunity and demonstrating that autoimmunity and antitumor immunity are not necessarily overlapping immune responses but can be decoupled at the cytokine level. IL-6 is only one cytokine, but this work offers proof of principle for taking the science to the next level by targeting multiple cytokines in a multi-layered approach," says Diab.

Source: Medindia