A panel of hot spot mutations is tested by target sequencing. Should a known HLA/mutant peptide pair be identified, the patient’s own T cells can be engineered by TCR gene therapy as an off-the-shelf strategy from a previously created library of TCRs. Alternatively, the patient’s TILs can be assessed for neoantigen reactivity by using a collection of mutant peptides from genes frequently mutated in human cancer and by using IFN-γ secretion or 41BB upregulation as a readout. These approaches will decrease the time requested to produce the engineered cell products or vaccine formulations for personalized therapy. Should the patient not harbor hot spot mutations in the tumor, the standard pipeline for neoantigen identification using whole-exome/RNA sequencing and epitope prediction is applied. Assessment of candidate peptides by T cell assays in vitro may be performed as an optional validation step.