Dendritic Cell Vaccine

Dendritic cells (DCs) are powerful antigen presenting cells for the induction of antigen specific T cell response[1]. DC vaccine has been introduced as a new therapeutic strategy in cancer patients. DC-based immunotherapy is relatively safe and can promote antitumor immune responses and prolonged survival of cancer patients.[2] An antigen-presenting cell vaccine is a vaccine made of antigens and antigen-presenting cells (APCs). Also called APC vaccine.

Non-activated (immature) DCs are usually located in the peripheral non-lymphoid tissues and they can present self-antigens to T cells, that leads to immune toleranceeither through T cell deletion or through the differentiation of regulatory T cells or suppressor T cells.[3]

Mature DCs have ability to present antigens in the lymphoid tissues and prime, activate and expand effector immune cells with unique functions and cytokine profiles.[4]

Myeloid or conventional DCs (cDCs) are derived from myeloid progenitor cells in the bone marrow and are characterized by expression of CD11c.[5] cDCs can be subdivided into 3 groups: monocyte-derived DCs, CD1a- interstitial DCs, and CD1a+ Langerhans cells.[6]

Plasmacytoid dendritic cells (pDCs) differentiate from lymphoid progenitor cells in the lymphoid tissues.[7] They express CD123 and product high levels of type I interferon.[8] pDCs also contribute to inflammatory responses in the steady state and in pathology. During inflammatory response, inflammatory DCs (iDCs) are generated from monocytes.[9]

The main goal of the therapeutic vaccines is to elicit cellular immunity.[10] They should prime naive T cells as well as induce transition from chronically activated non-protective CD8+ T cells to healthy CD8+ T cells able to produce cytotoxic T lymphocytes (CTLs), that recognise and eliminate cancer cells in an antigen-specific way and also provide long-lived memory CD8+ T cells that will act to prevent relapse.[11] The most critical step in vaccination is the effective presentation of cancer antigens to T cells and because of DCs are the most efficient antigen presenting cells, they are the promising option for improvement of therapeutic vaccines.[12]

DC-based immunotherapy approach can be employed in different ways

Most of trials testing in vivo DCs’ stimulation with synthetic peptides failed because of inability of effective stimulation of CD4+ cellular responses and stimulation of Th2 type cytokines.[13] The solution showing clinical responses was pre-treatment with single-dose cyclophosphamide as well as vaccination with tumor associated antigens (TAAs) and granulocyte macrophage colony stimulating factor (GM-CSF).[14]

In this way, DCs’ precursors are isolated from the patient through leukapheresis and after maturation/stimulation of these precursors ex vivo, fully mature DCs are injected back into the patient.[15] There are different ways applied to generate cancer cells-specific DCs. We can used specific TAAs, tumor lysates,created DC-cancer cell fusions, electroporation/transfection of DCs with total cancer cell-mRNA or tumor derived exosomes (TDEs) by the stimulation. There is also the possibility of additional co-stimulating with cytokine “cocktails” to assure strong maturation.[14]

The most well-known source of antigens used for vaccines in Glioblastoma (Aggressive type of brain tumor) investigations were whole tumor lysate, CMV antigen RNA and tumor associated peptides for instance EGFRvIII. The initial studies showed that patients developed immune responses as measured by Interferon-gamma expression in the peripheral blood, systemic cytokine responses, or CD8+ antigen specific T cell expansion. Clinical response rates were not as vigorous as the immune response rates. Overall survival (OS) and progression free survival (PFS) varied in different studies but were enhanced compared to historical controls.[16]

Sipuleucel-T is the first DCs- based cancer vaccine for men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (CRPC), approved by the US Food and Drug Administration (FDA) .[17][18] It is an active cellular immunotherapy, which involves obtaining antigen-presenting autologous dendritic cells from the patient following a leukapheresis procedure.[19] The cells are incubated ex vivo in the presence of a recombinant fusion protein PA2024 containing a prostate antigen, prostate acid phosphatase and GM-CSF, an immune-cell activator. The cells are then returned to the patient to generate an immune response.[20][21

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Exhibit A:  Anti-tumor vaccines (Generalities)

Exhibit B: Mechanisms of action with regard to the Dendritic Cell Vaccine

Exhibit C:  A cancer patient in a Mexican Cancer Clinic using Dendritic cell Therapy with ionic foot detox bath.

Open Access: This article incorporates public domain material from the U.S. National Cancer Institute and other public domain Governmental institutions.  This article is also distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this C.C. article which has been modified and improved by the ACR Institute for the benefit of the People’s fundamental right to benefit from equal  access to relevant knowledge that can significantly improve their chances of avoiding serious chronic diseases.
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