IgA as therapeutic antibody for cancer

Through (pre)clinical research, the AllIgAther consortium aims to add IgA to the arsenal of immunotherapies. By offering a unique, life-saving treatment for IgG-resistant or refractory patients, AllIgAther has the potential to greatly improve the curation of cancer.

Cancer is a major burden of disease worldwide. Each year, tens of millions of people are diagnosed with cancer, and more than half of them eventually die from it. Immunotherapies with monoclonal antibodies (mAb) employ the body’s immune system to target and destroy tumors and survival has improved. However, not all patients respond and often relapses occur.

All clinically available mAb are of the Immunoglobulin G class (IgG). However, IgA can be effective in vitro and in vivo, and has an alternative mechanism of action: IgA has the unique capacity activating neutrophils to kill cancer cells. Neutrophils are our most abundant but often underappreciated white blood cells. However, no IgA has been approved for systemic use in patients because it was hard to produce and purify IgA, it has a short half-life and mice lack the IgA receptor hampering preclinical research.

Recently, these issues were solved, allowing to prove the versatility of IgA mAb to treat cancer and to understand the underlying mechanism.

The deliverables of this project will be: 1) understanding of the working mechanism of IgA, 2) establish the effect of IgA on the tumor micro-environment, 3) demonstrate the effectiveness of IgA on resistant patients, and 4) quantification of the enhancement of IgA by blocking the neutrophil check point inhibitor SIRPa.