Immunogenicity and Safety of DCs in Breast Cancer
Condition: Breast Cancer Female
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study aims to evaluate for the first time in Colombia the immunogenicity and safety of
      autologous DCs as enhancers of the immune response in patients with ductal breast cancer who,
      prior to surgical resection of the tumor, will receive neo-adjuvant chemotherapy with
      Doxorubicin and Cyclophosphamide. concomitantly with the transfer of autologous DCs. This
      clinical trial is based on the concept proposed in countries like France more than a decade
      ago, that chemotherapy or radiotherapy cause the tumor cells to release certain signals that
      favor the activation of the immune system against cancer. Therefore, the combined use of
      chemotherapy with vaccination with dendritic cells would provide the immune system with
      greater antitumor response capacity, taking advantage of the release of said signals to
      initiate a series of processes that would be reflected in the activation of T lymphocytes
      capable of destroying the remaining cells of the tumor. To determine the specificity of the
      response evoked by the adoptive transfer of autologous DCs, in each patient the degree of
      recognition of the tumor by the immune system before and after said procedure will be
      evaluated. These results will be compared with those of patients who participated in a
      control group.

      Hypothesis Adoptive transfer of autologous DCs generated in vitro, in patients with stage
      IIA-IV breast cancer who receive neoadjuvant therapy with Doxorubicin and Cyclophosphamide,
      is a safe procedure that stimulates anti-tumor immune responses in treated patients.

      Principal aim:

      To evaluate the safety and immunogenicity of the use of DCs when used in patients with stage
      IIA-IV breast cancer in association with neo-adjuvant chemotherapy with
      Doxorubicin/Cyclophosphamide.

      Specific aims:

        -  Generate immuno-competent dendritic cells in conditions of Good Clinical Practice and
           Good Laboratory Practices.

        -  Determine in each patient the immunological status of specific T lymphocytes against
           tumor antigens, before and after chemotherapy, in order to demonstrate whether the
           adoptive transfer of DCs favors the anti-tumor immune response.

        -  Register in patients with breast cancer in neo-adjuvant chemotherapy the class and
           frequency of adverse effects that could be generated as a result of the adoptive
           transfer of autologous DCs.
    

Detailed description: 
      The Fundación Salud de los Andes in the framework of a strategic alliance with the National
      University of Colombia has been working in the planning and development of a clinical trial
      in Colombia that promotes the search for new therapeutic alternatives for cancer patients. As
      a translational medicine project, it aims to make the laboratory findings available to the
      patient. This study explores the combination of immunotherapy (cell therapy) with
      chemotherapy, in order to obtain better results in the therapeutic management of tumors in
      patients with breast cancer.

      Problem:

      Breast cancer is a pathology that in recent years has increased vertiginously its incidence
      globally. Given the advanced state in which this tumor is usually diagnosed in our
      environment, the prognosis is seriously compromised, which has led to the current breast
      cancer represents a major public health problem in Colombia. The established therapies for
      the management of patients with this type of tumors such as chemotherapy, radio-therapy or
      surgery, are effective to reduce much of the established tumor mass, but fail to eliminate
      residual cancer cells, so - often - these treatments cannot prevent the recurrence of the
      disease. In addition to the above, the quality of life of the patients treated is strongly
      affected by the toxicity of these treatments on healthy tissues and their undesirable
      effects, which frequently affects poor adherence to treatment. That is why it is necessary to
      search for new therapeutic alternatives that are more specific to the tumor and that are
      better tolerated by patients. Due to the high specificity of the immune system for the
      recognition of tumors, different modalities of immune therapy for tumor control are currently
      being explored, which seek to enhance the performance of the patient's defense system so that
      a cytotoxic and memory response is established against them. tumor cells.

      Type of study Clinical Trial Phase I / II.

      Methodology:

      Patients who attend the consultation due to their mammary pathology for the start of
      neo-adjuvant chemotherapy will be pre-selected to participate in the study. The participation
      of the volunteers will be subject to compliance with the inclusion and exclusion criteria
      defined for the study, as well as the signing of the informed consent. The participants will
      be randomly distributed into two groups.

      PATIENT GROUPS As part of the clinical evaluation at the entrance of the study, a battery of
      laboratory tests (basic and specific to the trial) will be carried out. Subsequent to the
      corroboration of compliance with the inclusion criteria, patients will be randomly assigned
      to one of the two study groups: The first group (A) will be the negative control group, which
      includes patients who will receive only the standardized chemotherapy treatment for the
      pathology. The second group (B) will consist of those patients who were randomly selected to
      receive the adoptive transfer of mature autologous DCs in combination with the neo-adjuvant
      chemotherapy. In this way, the total of 30 patients will be distributed as follows: 15
      patients for group A and 15 patients for group B.

      The patients of group B will undergo an apheresis procedure in order to obtain a sample
      enriched in peripheral blood monocytes from which monocytes will be purified for the
      production of DCs. The generation of DCs will be carried out under strict conditions of Good
      Clinical Practices and Good Laboratory Practices.

      The adoptive transfer will be carried out concomitantly with the neo-adjuvant chemotherapy
      treatment (eight and 15 days after chemotherapy dose for a total of 6 injections with
      autologous DCs).

      In the period of application of the doses, a permanent clinical evaluation will be carried
      out to the patients, to register possible adverse effects (evaluation of the safety of the
      adoptive transfer of autologous DCs). The effect on the immune response of autologous DCs
      transferred to patients on chemotherapy vs. the effect on the immune response of chemotherapy
      without transfer, will be analyzed in each patient before and after chemotherapy using the
      state of the art of immunological techniques with which will measure the extent of anti-tumor
      CD8+ T cells expansion (evaluation of the immunogenicity of the adoptive transfer of
      autologous DCs).

      Participating Institutions:

      Fundación Salud de los Andes Research Group in Immunology and Clinical Oncology - GIIOC

      National University of Colombia - Bogotá. School of Medicine Immunology and Translational
      Medicine Group Departments of Microbiology and Pathology

      Other collaborating institutions:

      Clínica del Seno Hospital Universitario Nacional Instituto Nacional de Cancerología Oncocare
    

Intervention name(s): Dendritic cells
Intervention type(s): Biological
Intervention description(s): Adoptive transfer of autologous DCs
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chemotherapy; Breast Cancer; Dendritic cells; Immunotherapy; Doxorubicine