The dendritic cell-based cancer vaccine is an innovation in therapeutic strategy for

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

patients. Dendritic cells (DCs) are

antigen presenting cells An antigen-presenting cell (APC) or accessory cell is a cell that displays an antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes u ...

for the induction of antigen specific

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

response. DC-based

immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

is safe and can promote antitumor

immune response An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellula ...

s and prolonged survival of cancer patients.

Human DC subsets

Immature dendritic cells

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 tolerance Immune tolerance, also known as immunological tolerance or immunotolerance, refers to the immune system's state of unresponsiveness to substances or tissues that would otherwise trigger an immune response. It arises from prior exposure to a specif ...

either through T cell deletion or through the differentiation of

regulatory T cell The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain immune tolerance, tolerance to self-antigens, and prevent autoimmune disease. Treg ...

Mature dendritic cells

Mature DCs have ability to present

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s in the lymphoid tissues, and to prime, activate, and expand immune effector cells with unique functions and

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

profiles.

Myeloid dendritic cells (cDCs)

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

Langerhans cell A Langerhans cell (LC) is a tissue-resident macrophage of the skin once thought to be a resident dendritic cell. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in t ...

Plasmacytoid dendritic cells (pDCs)

Plasmacytoid dendritic cell Plasmacytoid dendritic cells (pDCs) are a rare type of immune cell that are known to secrete large quantities of type 1 interferon (IFNs) in response to a viral infection. They circulate in the blood and are found in peripheral lymphoid organs. T ...

s (pDCs) differentiate from lymphoid progenitor cells in the

lymphoid tissue The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lympha ...

s. They express CD123 and product high levels of type I interferon. pDCs also contribute to inflammatory responses in the steady state and in pathology. During

inflammatory response Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

, inflammatory DCs (iDCs) are generated from

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...

Function of cancer therapeutic vaccines

The main goal of the therapeutic vaccines is to elicit cellular immunity. They should prime naïve T cell, and induce transition from chronically activated non-protective CD8⁺ T cells to healthy CD8⁺ T cells that can produce cytotoxic T lymphocytes (CTLs), which recognize and eliminate cancer cells by recognizing specific antigens. This process also creates long-lived memory CD8⁺ T cells that will act to prevent relapse. 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.

Methods for exploiting dendritic cells in cancer therapeutic vaccines

DC-based immunotherapy approach can be employed in two ways:

Direct targeting/stimulating of the DCs ''in vivo'' to accentuate their anticancer phenotype

Many trials evaluating ''in vivo'' DC stimulation with synthetic peptides failed because of inability of effective stimulation of CD4⁺ cellular responses and stimulation of Th2 type cytokines. 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).

Stimulation of the DCs ''ex vivo'' and infusing them back into the host for carrying out anticancer effector function

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. 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.

Dendritic cell vaccine against brain tumor

The most well-known source of antigens used for vaccines in

Glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nons ...

(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.

Dendritic cell vaccine against COVID-19

Autologous dendritic cells previously loaded ex-vivo with SARS-CoV-2 spike protein. Subjects eligible for treatment will be those who at baseline, are not actively infected with SARS-CoV-2, have no evidence of prior infection with SARS-CoV-2 based on serologic testing, and give informed consent for a vaccination with AV-COVID-19. The patient population will include the elderly and others at higher risk for poor outcomes after COVID-19 infection. For this reason, individuals will not be excluded solely on the basis of age, body mass index, history of hypertension, diabetes, cancer, or autoimmune disease.

Sipuleucel-T

Sipuleucel-T is the first DCs- based cancer vaccine for men with asymptomatic or minimally symptomatic metastatic castration-resistant

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

(CRPC), approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) . It is an active cellular immunotherapy, which involves obtaining antigen-presenting autologous dendritic cells from the patient following a leukapheresis procedure. 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.

References

{{reflist Cancer vaccines