Adjuvant Treatment for Breast Cancer Patients Using Individualized Neoantigen Peptide Vaccination—A Retrospective Observation

Breast cancer is a tumor entity that is one of the leading causes of mortality among women worldwide. Although numerous treatment options are available, current explorations of personalized vaccines have shown potential as promising new treatment options to prevent the recurrence of cancer. Here we present a small proof of concept study using a prophylactic peptide vaccination approach in four female breast cancer patients who achieved remission after standard treatment. The patients were initially analyzed for somatic tumor mutations and then treated with personalized neoantigen-derived peptide vaccines. These vaccines consisted of HLA class I and class II peptides and were administered intracutaneously followed by subcutaneous application of sargramostim and/or topical imiquimod as an immunological adjuvant. After an initial priming phase of four vaccinations within two weeks, patients received monthly boosting/maintenance vaccinations. Chemotherapy or checkpoint inhibition was not performed during vaccination. One patient received hormone therapy. The vaccines were well tolerated with no serious adverse events. All patients displayed vaccine-induced CD4+ and/or CD8+ T-cell responses against various neoantigens. Furthermore, all patients remained tumor-free and had persistent T-cell responses, even several months after the last vaccination, suggesting the potential of peptide vaccines as an immunosurveillance and long term prophylaxis option.

[1]  Elizabeth A. Peters,et al.  Editorial Board , 2014, Neuroscience Letters.

[2]  Yu Qin,et al.  Neoantigen: A New Breakthrough in Tumor Immunotherapy , 2021, Frontiers in Immunology.

[3]  S. Tolaney,et al.  Tumor mutational burden as a predictor of immunotherapy response in breast cancer , 2021, Oncotarget.

[4]  A. Stenzl,et al.  Use of plasma ctDNA as a potential biomarker for longitudinal monitoring of a patient with metastatic high-risk upper tract urothelial carcinoma receiving pembrolizumab and personalized neoepitope-derived multipeptide vaccinations: a case report , 2021, Journal for ImmunoTherapy of Cancer.

[5]  H. Redmond,et al.  The LOCalizer Radiofrequency Identification System: An Effective New Technology for Localizing Non-Palpable Breast Lesions for Surgery , 2020, Surgical innovation.

[6]  A. Iwasaki,et al.  Why and How Vaccines Work , 2020, Cell.

[7]  Ying S. Ting,et al.  A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer , 2020, Cell.

[8]  S. Biskup,et al.  A Highly Specific Assay for the Detection of SARS-CoV-2–Reactive CD4+ and CD8+ T Cells in COVID-19 Patients , 2020, The Journal of Immunology.

[9]  J. Lai,et al.  Peptide-Based Vaccines: Current Progress and Future Challenges , 2019, Chemical reviews.

[10]  E. Mittendorf,et al.  Efficacy and Safety Analysis of Nelipepimut-S Vaccine to Prevent Breast Cancer Recurrence: A Randomized, Multicenter, Phase III Clinical Trial , 2019, Clinical Cancer Research.

[11]  R. Hollingsworth,et al.  Turning the corner on therapeutic cancer vaccines , 2019, npj Vaccines.

[12]  L. Wilson,et al.  Is Proton Therapy a “Pro” for Breast Cancer? A Comparison of Proton vs. Non-proton Radiotherapy Using the National Cancer Database , 2019, Front. Oncol..

[13]  K. To,et al.  Recent Advances in the Treatment of Breast Cancer , 2018, Front. Oncol..

[14]  H. Rammensee,et al.  Personalized cancer vaccines: adjuvants are important, too , 2018, Cancer Immunology, Immunotherapy.

[15]  Li Ding,et al.  Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines. , 2018, Cell systems.

[16]  M. Schubach,et al.  Immune monitoring and TCR sequencing of CD4 T cells in a long term responsive patient with metastasized pancreatic ductal carcinoma treated with individualized, neoepitope-derived multipeptide vaccines: a case report , 2018, Journal of Translational Medicine.

[17]  J. Utikal,et al.  Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer , 2017, Nature.

[18]  Charles H. Yoon,et al.  An immunogenic personal neoantigen vaccine for patients with melanoma , 2017, Nature.

[19]  S. Siesling,et al.  Patterns and predictors of first and subsequent recurrence in women with early breast cancer , 2017, Breast Cancer Research and Treatment.

[20]  G. Viale,et al.  An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper® , 2017, Breast Cancer Research.

[21]  I. Mellman,et al.  Neo approaches to cancer vaccines , 2015, Science.

[22]  E. Mardis,et al.  A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells , 2015, Science.

[23]  Benjamin Schubert,et al.  OptiType: precision HLA typing from next-generation sequencing data , 2014, Bioinform..

[24]  D. McNeel,et al.  Real-Time Immune Monitoring to Guide Plasmid DNA Vaccination Schedule Targeting Prostatic Acid Phosphatase in Patients with Castration-Resistant Prostate Cancer , 2014, Clinical Cancer Research.

[25]  A. Chicheł,et al.  Brachytherapy in breast cancer: an effective alternative , 2014, Przeglad menopauzalny = Menopause review.

[26]  Hiroaki Tanaka,et al.  Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival , 2012, Nature Medicine.

[27]  E. Mardis,et al.  Cancer Exome Analysis Reveals a T Cell Dependent Mechanism of Cancer Immunoediting , 2012, Nature.

[28]  C. Slingluff The present and future of peptide vaccines for cancer: single or multiple, long or short, alone or in combination? , 2011, Cancer journal.

[29]  Päivi Heikkilä,et al.  Subtyping of Breast Cancer by Immunohistochemistry to Investigate a Relationship between Subtype and Short and Long Term Survival: A Collaborative Analysis of Data for 10,159 Cases from 12 Studies , 2010, PLoS medicine.

[30]  Melissa Bondy,et al.  Residual risk of breast cancer recurrence 5 years after adjuvant therapy. , 2008, Journal of the National Cancer Institute.

[31]  S. Morrison,et al.  Prospective identification of tumorigenic breast cancer cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[32]  N. Shastri,et al.  Producing nature's gene-chips: the generation of peptides for display by MHC class I molecules. , 2002, Annual review of immunology.

[33]  I. Barillot,et al.  Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. , 2001, The New England journal of medicine.

[34]  I. Weissman,et al.  Stem cells, cancer, and cancer stem cells , 2001, Nature.

[35]  D. Dunlop RECENT ADVANCES IN TREATMENT , 1955 .