Reference
Reference TypeLiterature
IEDB_Reference:1045769
TitleA neoantigen vaccine generates antitumour immunity in renal cell carcinoma.
AuthorsDavid A Braun; Giorgia Moranzoni; Vipheaviny Chea; Bradley A McGregor; Eryn Blass; Chloe R Tu; Allison P Vanasse; Cleo Forman; Juliet Forman; Alexander B Afeyan; Nicholas R Schindler; Yiwen Liu; Shuqiang Li; Jackson Southard; Steven L Chang; Michelle S Hirsch; Nicole R LeBoeuf; Oriol Olive; Ambica Mehndiratta; Haley Greenslade; Keerthi Shetty; Susan Klaeger; Siranush Sarkizova; Christina B Pedersen; Matthew Mossanen; Isabel Carulli; Anna Tarren; Joseph Duke-Cohan; Alexis A Howard; J Bryan Iorgulescu; Bohoon Shim; Jeremy M Simon; Sabina Signoretti; Jon C Aster; Liudmila Elagina; Steven A Carr; Ignaty Leshchiner; Gad Getz; Stacey Gabriel; Nir Hacohen; Lars R Olsen; Giacomo Oliveira; Donna S Neuberg; Kenneth J Livak; Sachet A Shukla; Edward F Fritsch; Catherine J Wu; Derin B Keskin; Patrick A Ott; Toni K Choueiri
AffiliationsSection of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA. david.braun@yale.edu; Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. david.braun@yale.edu; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. david.braun@yale.edu; Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark; Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Urology, Brigham and Women's Hospital, Boston, MA, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA; Center for Cutaneous Oncology, Dana-Farber Brigham and Women's Cancer Center, Boston, MA, USA; Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Genomic Medicine, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark; Molecular Diagnostics Laboratory, Department of H...
JournalNature
PMID:39910301
Year2025
AbstractPersonalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens<sup>1-6</sup>. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient's tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 months after surgery, none of the 9 participants enrolled in the study had a recurrence of RCC. No dose-limiting toxicities were observed. All patients generated T cell immune responses against the PCV antigens, including to RCC driver mutations in VHL, PBRM1, BAP1, KDM5C and PIK3CA. Following vaccination, there was a durable expansion of peripheral T cell clones. Moreover, T cell reactivity against autologous tumours was detected in seven out of nine patients. Our results demonstrate that neoantigen-targeting PCVs in high-risk RCC are highly immunogenic, capable of targeting key driver mutations and can induce antitumour immunity. These observations, in conjunction with the absence of recurrence in all nine vaccinated patients, highlights the promise of PCVs as effective adjuvant therapy in RCC.
Curation Last Updated2025-03-17 22:29:30
Epitope
Epitope ID2274549
IEDB_epitope:2274549
Chemical TypeLinear peptide
Linear SequenceSQEHPPPHIQLLSAMA
Epitope Reference Details
Epitope Structure DefinesEpitope containing region/antigenic site
Epitope NameSQEHPPPHIQLLSAMA
Location of Data in ReferenceSupplementary Table 2
Epitope Related Object
Related Object Typeframeshift neo-epitope
Chemical TypeLinear peptide
Linear SequenceSQEHPPP
Source Molecule Nameangiomotin like 2 [Homo sapiens]
GenPept:KAI2531582.1
Source OrganismHomo sapiens (human)
NCBITaxon:9606
Starting Position326
Ending Position332
Immunization
Host OrganismHomo sapiens (human)
NCBITaxon:9606
Host Details
Host Geolocationcontiguous United States of America
GAZ:00003937
Age50.4-75.7 years
1st In Vivo Process
In Vivo Process TypeOccurrence of cancer
ONTIE:0003320
Disease Staterenal cell carcinoma
DOID:4450
Disease StageCancer Stage III;Cancer Stage IV;Metastatic;NCIT:C27970;NCIT:C27971;NCIT:C14174
2nd In Vivo Process
In Vivo Process TypeTherapeutic vaccinationVO:0005373
2nd In Vivo Process Administration Details
Dose Schedule5 priming doses of 300 µg on days 1, 3, 8, 15, and 22 followed by boosts on day 78 and 134
2nd Immunogen
Epitope RelationEpitope
Chemical TypeLinear peptide
Linear SequenceSQEHPPPHIQLLSAMA
Immunogen Details
Immunogen Evidence CodeExact match to reference information
In Vitro Administration
In Vitro Process TypeRestimulation in vitro
Responder Cell TypePBMC
CL:2000001
Stimulator Cell TypePBMC
CL:2000001
In Vitro Immunogen
In Vitro Process TypeEpitope
Chemical TypeLinear peptide
Linear SequenceSQEHPPPHIQLLSAMA
Immunization Comments
Immunization CommentsPatients were immunized s.c. and i.d. with the epitope adjuvanted with poly IC:LC as part of a peptide pool. Week 16 PBMC were restimulated with the epitope as part of a peptide pool.
T Cell Assay
Qualitative MeasurementNegative
Method/TechniqueELISPOT
OBI:1110059
Measurement ofIFNg release
Effector Cells
Effector Cell Tissue TypeBlood
UBERON:0000178
Effector Cell TypePBMC
CL:2000001
Effector Cell Culture ConditionsShort Term Restimulated
Antigen Presenting Cells
Cell Tissue TypeBlood
UBERON:0000178
Cell TypePBMC
CL:2000001
Cell Culture ConditionsDirect Ex Vivo
Antigen
Epitope RelationEpitope
Chemical TypeLinear peptide
Linear SequenceSQEHPPPHIQLLSAMA
Assay Reference Details
Location of Assay Data in ReferenceFigure 2, Extended Data Figure 2, and Supplementary Table 2