Modulation of antibody-dependent cancer therapy

Antibody therapy is increasingly used in the treatment of cancer. Louise Treffers investigated how antibodies exactly contribute to the destruction of cancer cells by a certain type of immune cell, the neutrophil granulocyte. Her research contributes to improving this promising therapy. Thesis defense: 26 October 2020.

Therapeutic antibodies directed against tumor cells are increasingly being used in the treatment of various forms of cancer. Because the extent to which patients benefit from this form of immunotherapy varies greatly, it is important to know exactly how these tumor-focused therapeutic antibodies work, and how their efficacy can be further improved.

The research described in this thesis was done to better understand how our most common white blood cell, the neutrophil granulocyte, contributes to the destruction of cancer cells when using antibodies. First of all, we found that the type of antibody is important, with so-called IgA antibodies, for example, outperforming the most commonly used IgG antibodies. The relative ineffectiveness of IgG antibodies turned out to be partly due to the occurrence of a unique receptor for antibodies on granulocytes that hinders the recognition and destruction of antibody-coated tumor cells.

In addition, genetic variations in the protein structure of such antibody receptors appeared to play a critical role. Finally, the destruction of cancer cells using antibodies was shown to be enhanced by inhibition of CD47-SIRP interactions.

These results provide opportunities to improve immunotherapy with antibodies directed against cancer cells. The first clinical studies combining antibodies against cancer cells with CD47-SIRP inhibitors have already shown promising results.

Promotores: Prof TK van den Berg PhD and prof TW Kuijpers MD PhD
Copromotor: HL Matlung PhD

Venue: Aula Vrije Universiteit  (invitation only) and on-line