癌症疫苗的未来.pdf

1、The Future of Cancer VaccinesClinical Director,Melanoma CenterDana Farber Cancer InstituteProfessor of MedicineHarvard Medical SchoolDisclosuresAdvisory Role:Alexion,Array,Bristol-Myers Squibb,Celldex,CytomX,Genentech,Merck,Neon Therapeutics,Novartis,Pfizer,TRM Oncology,Evaxion,Immunetune,Servier,My

2、Neo,PhioGrants to institution:Armo Biosciences,AstraZeneca/MedImmune,Bristol-Myers Squibb,Celldex,CytomX,Genentech,Merck,Neon Therapeutics,Novartis,Pfizer Hu Ott Wu Nature Reviews Immunology 2018Objective of a Cancer Vaccine:Elicit,expand,diversify tumor-specific T-cell responses to induce long last

3、ing anti-tumor immunityShared One neoantigen(driver mutation)Shared Several Neoantigens pooled(driver mutations)Personalized Neoantigens(driver,passenger mutations)Shared vs.Personalized Neoantigen VaccinesNeoVax:Key findings from initial clinical trialsTumor infiltrating T cellsPre-vaxPost-vaxNeoan

4、tigen-reactive T cells from peripheral bloodKeskin et al Nature 2019Vax-specific T cells traffic to tumorsOtt et al Nature 2017Mutant Vax-specific ex vivo T cells responsesSFU/106SFU/106Hu al.Nature Med 2021NeoVax:Key findings from initial clinical trialsOtt al.Cell 2020 xxEpitope Spread in pts with

5、 long PFSComplete path CR after vaxT cell immunity induced with a Personalized RNA vaccine+Atezolizumab+mFOLFORINOX in half of the patientsRojas,Nature,2023Lopez,Nature,2023T cell immunity induced with a Personalized RNA vaccine+Atezolizumab+mFOLFORINOX correlates with delayed recurrenceSethna,Natur

6、e,2025Randomized Phase 2 trial:mRNA-4157+pembrolizumab vs.Pembrolizumab alone PCV clinical trials landscape:Completed(results)vs.Ongoing(no results)020040060080010001200PatientsTrialsCompleted versus ongoing PCV Trials020040060080010001200PatientsTrialsCompleted versus ongoing PC