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After surgery and removal of the tumor, massively parallel sequencing (via whole-exome and RNA sequencing) can be used to identify the mutational spectrum of the patient's tumor. A pool of potential mutated peptide epitopes deduced from the sequencing data can then be used directly, or predictions in silico can help select the most immunogenic ones. These epitopes are incorporated into a vaccine formulation and then used in conjunction with other agents to enhance immune response, including antibodies that block negative immune checkpoints such as CTLA-4 and PD-1. During the time needed for vaccine preparation, the patient may receive standard-of-care therapy to achieve minimal residual disease (MRD) in the adjuvant setting or to achieve clinical remission or disease stabilization in advanced disease. If patients progress or relapse after vaccination, tumor samples can be biopsied to evaluate potential immune escape mechanisms, such as antigen or MHC loss, to guide improvements in the strategy. MPS, massively parallel sequencing.
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