Timeline of key milestones and technological advances in neoantigen-based cancer immunotherapy

YearMilestoneImpact on cancer researchKey technologiesTherapeutic applicationsReferences
1950sImmune recognition of carcinogen-induced tumorsRole of immune system in tumor detectionNoneEarly understanding[32, 33]
1980sT cell recognition of neoantigens in miceCellular immune mechanismsMurine modelsNone[14, 34]
1990sConfirmed neoantigen reactivity in miceEvidence for tumor-specific immune responsesMurine modelsNone[35, 36]
1990sNeoantigen reactivity in human cancersBroadened immune detectionHuman tumor modelsNone[13]
2000sNeoantigen reactivity in CD4+ T cellsIdentified immune cell responsesFlow cytometryNone [37]
2000sIdentified neoantigen-reactive T cells in melanoma patientsEnhanced clinical relevanceFlow cytometryNone[38, 39]
2000sNeoantigen reactivity over shared antigensClarified neoantigen advantageHuman tumor modelsNone[40]
2010sNGS for immunogenic neoantigen identificationAccelerated antigen discoveryNGSNone[41, 42]
2010sNGS for neoantigen-reactive T cells in melanomaMapped T cell specificityNGS, flow cytometryNone[43, 44]
2010sNeoantigen-based adoptive cell therapy in GI cancerFirst clinical applicationNGS, adoptive cell therapyGI cancer treatment[45, 46]
2010sPersonalized neoantigen vaccines for melanomaPioneered patient-specific vaccinesNGS, peptide synthesisMelanoma treatment[47, 48]
2010sKRAS neoantigen adoptive cell therapy in colorectal cancerTargeted oncogene mutationsNGS, adoptive cell therapyColorectal cancer treatment[49, 50]
2010sPersonalized neoantigen peptide and RNA vaccinesAdvanced specificity and delivery methodsNGS, RNA technologyMultiple tumor types[51, 52]

NGS: next-generation sequencing; GI: gastrointestinal