Autologous dendritic cells and activated cytotoxic T‑cells as combination therapy for breast cancer

Abstract

Breast cancer is the most common oncological pathology in women worldwide. Techniques for improving the clinical parameters of patients undergoing combination therapy for breast cancer are currently under development. A type of treatment employing dendritic cells (DCs) and cytotoxic DC-induced antigen-specific T lymphocytes efficiently eliminates residual cancer cells that are the key cause of tumor recurrence and metastasis. In the present study, DCs and activated lymphocytes (treated with IL-12 and IL-18) were isolated from the peripheral blood of patients with breast cancer, using a lysate of tumor tissue as antigen. The patients received the cells as part of adjuvant or neoadjuvant regimens (stage IV disease or progression). Evaluation of immunity was performed at 3 and 6 months after terminating immunotherapy. Evaluation of the disease-free period was performed for 3 years after surgery. The use of antigen-loaded autologous DCs combined with mononuclear cells with increased cytotoxic activity following Th1 polarization reduced the populations of immunosuppressive cells. The results of the present study demonstrated that the investigated cellular immunotherapy for breast cancer is safe, reduces the risk of relapse and metastasis, and improves immunity by reducing the number of regulatory T cells. Therefore, this therapeutic strategy may represent a novel approach to combating distant metastases of breast cancer.

Dendritic cells transfected with a polyepitope DNA construct stimulate an antitumor cytotoxic response in various tumor diseases

“…In terms of cytotoxicity generated, the results of current research showed comparable efficiency levels comparing with the HER2/neu protocol, thus we can state that the use of DNA constructs encoding the wide range of TAA epitopes can also be efficient in stimulation of antitumor T-cell response, but the wide range of TAA epitopes enables the use of such approach in treatment of more cancer types. We also previously tested a protocol for generation of antigen-primed DCs in breast cancer patients in vivo [13]. There we used autologous tumor cell lysate as an antigen source and showed the increase in the count of CD8+ cells, which exhibit strong antitumor cytotoxic activity [13].…”

“…We also previously tested a protocol for generation of antigen-primed DCs in breast cancer patients in vivo [13]. There we used autologous tumor cell lysate as an antigen source and showed the increase in the count of CD8+ cells, which exhibit strong antitumor cytotoxic activity [13]. In this regard, we see that autologous tumor lysate can also be a viable option for DC antigen loading, but here we should take into account that lysate requires the preparation of tumor material for every patient separately, and in lots of cases, tumor tissues are not available.…”

“…Transferring the whole process of the endogenous immune response activation ex vivo, outside the immunosuppressive tumor influence, is shown to be feasible in obtaining T-cells efficient for tumor elimination when administered to patients as part of combination therapy [20,13]. Herewith, a number of studies have confirmed the effectiveness of DC antigen loading using DNA constructs [5][6][7][8].…”

Breast cancer treatment by transplantations of dendritic cells and cytokine-induced killer cells: An update on clinical trials

“…Stimulation activity of DCs is through the ability to capture, processing and presenting a tumorassociated antigen (TAAs), which induces specific antitumor responses. The intervention combining DCs and T cells ex vivo resulted in a lower risk of relapse and metastasis, lower level of T-reg, and increased Th1 polarization in breast cancer patients 67 . In recent years, several studies have reported that the synergistic antitumor effect of CIK blends with DCs 13,21, 68 .…”

Advanced therapeutic modalities in hepatocellular carcinoma: Novel insights

“…However, particular tumour conditions, such as limited access to TAAs, prevent DCs from functioning properly. 75 Bioengineered DCs with toll-like receptor (TLR) agonists, TAAs, TAA-derived peptides and tumour lysates have recently been developed as novel vaccines and are broadly used in treating breast cancer, 76 lung cancer, 77 prostate cancer 78 and HCC. [79][80][81] A phase I/II clinical trial assessed intradermal immunization with DC-based vaccines.…”