Immunogenicity and Safety of DCs in Breast Cancer

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