Personalized Vaccine for Cancer Immunotherapy
Condition: Breast Cancer Female
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      Due to their genetic instability, breast tumors that do not express receptors for Estrogens,
      Progestagens or amplify the Her2 / neu oncogene [called triple-negative breast cancer (TNTC)]
      and other tumors such as melanoma, non-small cell lung cancer, accumulate numerous mutations
      that make them highly resistant to different regimens of chemo- or radiotherapy, thereby
      generating high morbidity and mortality. However, immunology can turn the genetic instability
      of tumors into the Achilles' tendon. Evidence of this has been revealed in Phase I clinical
      studies in patients with melanoma and lung cancer in an advanced stage of metastasis treated
      with Ipilimumab (anti-CTLA4) to decrease immunosuppression, in whom peptides containing
      mutations presented in Major Complex molecules Histocompatibility of Class I (HCM I) of the
      tumor itself results in their recognition as "foreign" neo-antigens leading to the efficient
      destruction of the tumor by anti-tumor CD8 + T lymphocytes that are amplified when they are
      vaccinated with these peptides.

      For this reason, the identification of non-synonymous mutations of single amino acid and
      vaccination with 25 amino acid peptides that incorporate these mutations (synthetic vaccines)
      is emerging today as an alternative for immunotherapy of cancers responsible for high
      mortality in humans. In an approach that takes 16 weeks, today, it is possible to go from the
      analysis of the tumor's transcriptome (which allows identifying the universe of tumor
      mutations) to the patient's vaccination with a personalized vaccine that contains
      neo-antigens of his tumor.

      TNBC is the most aggressive breast tumor, representing around 25% of breast cancers in our
      environment. While generally, at least 30% of women with other types of metastatic breast
      cancer survive 5 years after diagnosis, most patients diagnosed with metastatic CMTN die
      within this time. The lack of selective therapies and the poor prognosis of patients with
      NTMC make their therapeutic management difficult, so the implementation of new therapies for
      this type of tumor is the main focus of researchers who seek more effective and selective
      treatments to improve the life expectancy of patients without compromising their quality of
      life. The genetic instability and high rate of mutations of the TNBC most likely favor the
      generation of neo-epitopes. Still, due to the immunosuppressive environment of the tumor, it
      escapes the immunosurveillance of the immune system. Despite the high mortality induced by
      this tumor, a percentage of patients treated with neoadjuvant chemotherapy with agents such
      as Doxorubicin and Cyclophosphamide (AC) + Taxanes respond to this chemotherapy regimen. In
      particular, the anti-tumor effect of AC is attributed to two things: (i) the direct cytotoxic
      effect on the tumor cell, (ii) the immunostimulation of T lymphocytes promoted by Immunogenic
      Cell Death (ICM) selectively induced by these drugs. Therefore, in this project, we propose
      to carry out the first clinical study in Colombia of vaccination of patients with TNBC with
      synthetic peptides that contain mutations of their own tumor to evaluate the immunogenicity
      and safety of this type of personalized vaccine as a therapeutic alternative for this tumor.
      Achieving the specific objectives set out in this project would mean that we have been
      validated in Colombia the experimental design necessary to identify unique epitopes in tumors
      and demonstrate the safety and immunogenicity of these vaccines. We consider that having
      achieved the above; we will have taken an important step towards the implementation in our
      country of the use of this type of vaccine for immunotherapy not only of TNBC but of other
      tumors such as glioblastoma, gastric, esophagus, and pancreas, highly fatal due to its high
      mutation rate.
    


Intervention name(s): Peptide pulsed Dendritic cell
Intervention type(s): Biological
Intervention description(s): Intradermal vaccination with peptide-pulsed autologous dendritic cells in 200 µL of patient's serum in six doses weekly after surgery.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Triple negative breast cancer; Neo-adjuvant chemotherapy; Dendritic cells; Peptide; Immunotherapy; Immune-monitoring; Personalized vaccines