Novel Immunotherapy Approach Holds Promise for Pediatric Brain Cancer

May 26, 2020 | Biotechnology

Reading time: 3-4 minutes

To keep you updated on current Biotechnology industry news, Lab.Equipment has curated this article from Genetic Engineering and Biotechnology News (GEN) for you:

Scientists at Sanford Burnham Prebys say they have discovered that combining immunotherapy with tumor necrosis factor (TNF) eradicated a deadly type of pediatric brain tumor in mice. Their study “Tumor necrosis factor overcomes immune evasion in p53-mutant medulloblastoma”, published in Nature Neuroscience, is expected to lead to a clinical trial to test the benefits of the treatment in patients. The findings also hold implications for other cancers that do not respond to immunotherapy.

“Many immunotherapies act by enhancing the ability of cytotoxic T cells to kill tumor cells. Killing depends on T cell recognition of antigens presented by class I major histocompatibility complex (MHC-I) proteins on tumor cells. In this study, we showed that medulloblastomas lacking the p53 tumor suppressor do not express surface MHC-I and are therefore resistant to immune rejection. Mechanistically, this is because p53 regulates expression of the peptide transporter Tap1 and the aminopeptidase Erap1, which are required for MHC-I trafficking to the cell surface,” write the investigators.

“In vitro, tumor necrosis factor (TNF) or lymphotoxin-β receptor agonist can rescue expression of Erap1, Tap1 and MHC-I on p53-mutant tumor cells. In vivo, low doses of TNF prolong survival and synergize with immune checkpoint inhibitors to promote tumor rejection. These studies identified p53 as a key regulator of immune evasion and suggest that TNF could be used to enhance sensitivity... More of this in the GEN Blog.

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