Pediatric multicellular tumor spheroid models illustrate a therapeutic potential by combining BH3 mimetics with Natural Killer (NK) cell-based immunotherapy

• DOI: 10.1038/s41420-021-00812-6
• Publication Date: 2022-01-10T11:03:42Z
• Authors: Vinzenz Särchen; Senthan Shanmugal...; Sarah Kehr; Lisa Marie Reindl; Victoria Greze; Sara Wiedemann; Cathinka Boedicker; Maureen Jacob; Katrin Bankov; Nina Becker; Sibylle Wehner; Till M. Theilen; Steffen Gretser; Elise Gradhand; Carsten Kummerow; Evelyn Ullrich; Meike Vogler
• Keywords: Spheroid; Multicellular organism; Lymphokine-activated killer cell

The induction of apoptosis is a direct way to eliminate tumor cells and improve cancer therapy. Apoptosis tightly controlled by the balance pro- antiapoptotic Bcl-2 proteins. BH3 mimetics neutralize function proteins are highly promising compounds inducing in several entities including pediatric malignancies. However, clinical application solid tumors impeded frequent resistance single anticipated toxicity high concentrations or combination treatments. One potential avenue increase potency development immune cell-based therapies counteract intrinsic sensitize them attack. Here, we describe spheroid cultures that can serve as models for drug testing. In these 3D models, were able demonstrate activated allogeneic Natural Killer (NK) migrated into spheroids displayed cytotoxicity against wide range spheroids, highlighting their anti-tumor effector cells. Next, investigated whether treatment with subtoxic NK Notably, cytotoxic effects enhanced addition mimetics. Treatment either Bcl-XL inhibitor A1331852 Mcl-1 S63845 increased reduced size, while ABT-199 had no effect on cell-mediated killing. Taken together, this first study targeting immunotherapy, immunotherapy.