SITC 2022 | Improving anti-CTLA4 efficacy in neuroblastoma via the induction of mismatch repair deficiency

Saman Maleki, PhD, Western University, London, Canada, talks on improving immunotherapy for neuroblastoma tumors, a form of childhood cancer. Neuroblastoma tumors are often non-immunogenic and very aggressive and do not tend to respond to immune checkpoint inhibitors (ICIs). Tumors with mismatch repair deficiency tend to respond better to ICIs, and so mismatch repair deficiency was induced into the neuroblastoma tumors via knocking out MLH1. Subsequently, the neuroblast tumors became responsive to immunotherapy with anti-CTLA4, but not anti-PD1. Using preclinical models, it was found that anti-CTLA4 therapy in neuroblastoma tumors with induced DNA mismatch repair deficiency had depleted Tregs and expanded ICOS+ T-cells. This interview took place at the 37th Annual Meeting of the Society for Immunotherapy in Cancer (SITC 2022) in Boston, MA.

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