Breast Cancer Neoantigen Vaccination With Autologous Dendritic Cells
Condition: Breast Cancer; Triple Negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      In this project, the investigators propose the first clinical study in Colombia of
      vaccination of patients with triple-negative breast cancer (TNBC) using synthetic peptides
      that contain mutations of the tumor itself that will be presented to the immune system by
      autologous dendritic cells to assess immunogenicity and safety of this type of personalized
      vaccine. Achieving the specific objectives set out in this project will mean that the
      investigators can validate in Colombia the experimental design necessary to identify
      exclusive epitopes in the tumors of the participants in this study, and also that have been
      able to demonstrate the safety and immunogenicity of these vaccines.
    

Detailed description: 
      EXECUTIVE SUMMARY.

      The achievements of personalized medicine in cancer research in developed countries make
      envision that various types of cancer in an advanced stage, will be in the medium term
      treatable diseases. The discovery of new therapies is the product of the achieved development
      of Translational Medicine (the laboratory findings translated in short term to the patient
      benefits), a new approach to applied medicine led by researchers in the universities in
      alliance with the private sector who carry out clinical studies. Despite the advances of
      Personalized and Translational Medicine in the developed world in Colombia, this discipline
      has an incipient development.

      Due to its genetic instability, triple-negative breast cancer - (CMTN) (ER-, PR-, Her2 /
      neu-) among other tumors with a high number of mutations makes it resistant to
      chemotherapy/radiotherapy regimens generating high morbidity and mortality. Furthermore,
      genetic instability contributes not only to the immuno-editing of these tumors [5] but to the
      generation of a suppressive tumor microenvironment [6], which are factors that contribute to
      the escape of these tumors to their immunosurveillance [7, 8]. However, recent achievements
      suggest that these factors are controllable using personalized medicine. While
      immunosuppression is modulated with the use of anti-checkpoint antibodies ("anti-check
      points" such as anti-CTLA4, anti-PD1, and anti-PDL-1) [9], genetic instability that generates
      tumor neoantigens, may become the Achilles' heel of these tumors. Phase I clinical studies of
      patients with melanoma and lung cancer metastatic treated with Ipilimumab (anti-CTLA4 of
      anti-PD1) - to decrease immunosuppression - using together with vaccines peptides
      corresponding to tumor mutations that are presented in MHCI and MHCII molecules and are
      recognized by LT-CD8 as foreign antigens, led these cells to destroy the tumor efficiently
      when used as a vaccine [10-13]. For this reason, the identification of non-synonymous
      mutations of single amino acid and vaccination with 25 amino acid peptides incorporating
      these mutations (synthetic vaccines), is emerging as an alternative for cancer immunotherapy
      [10-13] in what is called neoantigen based synthetic cancer vaccines. In an approach that
      takes 16 weeks, today it is possible to go from the analysis of the tumor transcriptome to
      identify the universe of tumor mutations up to the vaccination of the patient with peptides
      containing tumor mutations, with the important clinical response to the tumor not achieved so
      far in patients with melanoma and non-small cell carcinoma of the metastatic lung [10-13].
      Therefore, we propose to carry out the first clinical study in Colombia of vaccination of
      patients with CMTN using synthetic peptides that contain mutations of the tumor itself that
      will be presented by autologous dendritic cells in order to evaluate the immunogenicity and
      safety of this type of personalized vaccine. Achieving the specific objectives set out in
      this project will mean that we have validated in Colombia the experimental design necessary
      to identify unique epitopes in each tumor of the participants in the study in addition to
      demonstrating the safety and immunogenicity of these vaccines. Once this has been achieved,
      we consider having taken an important step towards implementation in our country of the use
      of this type of vaccine for immunotherapy not only of CMTN but of other highly fatal tumors
      such as glioblastoma, gastric, esophagus, and pancreas.

      This project is carried out by the National University, the Hospital El Tunal de Bogotá, and
      the Fundación Salud de los Andes, has the collaboration of Professor Luis Fernando Niño and
      Andrés Pinzón, experts in bioinformatics in the Universidad Nacional; Dr. Chris Miller at
      Washington University at the McDonnell Genomic Institute at Washington University, School of
      Medicine in Saint Louis; has the advice of Dr. Pedro Romero from the University of Lausanne
      (Switzerland) who has extensive experience in immunotherapy clinical trials of melanoma
      patients with synthetic peptides as a vaccine and with researchers from the Research Group in
      Immunology and Clinical Oncology (GIIOC) of the Fundación Salud de los Andes.
    

Intervention name(s): Neo-antigen pulsed Dendritic cell
Intervention type(s): Biological
Intervention description(s): Patients that have already finished their conventional treatment (chemotherapy and/or surgery) will be vaccinated with dendritic cells pulsed with synthetic peptide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Dendritic cells; Neo-antigen; Personalized medicine; immunotherapy