Although both antigen types present as attractive targets for the development of cancer-eradicating immunotherapies, expression of TAAs in normal cells can trigger central and peripheral tolerance mechanisms that ultimately lead to selection of T cells with low-affinity receptors. Attempts to combat this effect through targeting of TAAs via high-affinity T cell receptors have been found to result in severe toxicities due to normal tissue destruction (Parkhurst et al. 2011). Unlike TAAs, tumor-specific neoantigens are not subject to central or peripheral tolerance and lack the ability to destroy normal tissues since their mutations arose from the tumor itself (Lu et al. 2016). Due to this key difference in the development of these antigens, the researchers will use tumor-specific neoantigens for the identification and subsequent targeting of pancreatic cancer cells through immunotherapy.
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