What are dendritic cells?
Dendritic cells are among the most important antigen-presenting cells of the immune system. They take up antigens and components of altered cells, process them and present characteristic structures to T cells via MHC molecules.
In this way, they form a functional link between early immune recognition and a targeted adaptive immune response. The uptake of an antigen alone is not decisive; the maturation state of the dendritic cell, co-stimulation and the surrounding immunological environment are also important.
Antigen Uptake
Dendritic cells take up proteins, cellular components and tumour-associated antigen structures.
Processing
The material taken up is processed and prepared for antigen presentation.
T-Cell Activation
Antigen presentation and co-stimulatory signals can support a specific T-cell response.
2011 Nobel Prize
Ralph M. Steinman received one half of the 2011 Nobel Prize in Physiology or Medicine for his discovery of the dendritic cell and its role in adaptive immunity. This discovery provided an important foundation for modern vaccine and immunotherapy concepts.
What does dendritic cell therapy mean?
In patient-specific dendritic cell therapy, suitable starting cells are collected and developed into dendritic cells under controlled laboratory conditions. They are then exposed to the intended tumour-associated antigen source, matured, quality-controlled and administered after release.
The specific procedure may vary depending on the starting material, antigen source, maturation protocol, tumour type, disease stage and accompanying treatment measures. Individual medical and laboratory-specific planning is therefore required.
Manufacturing in a GMP laboratory
Manufacturing is carried out according to a documented and controlled procedure. Product-specific processing steps and release criteria are defined by the responsible laboratory.
Initial medical assessment
Review of the diagnosis, general condition, blood count, current therapies, infections, organ function and possible exclusion criteria.
Blood Collection
Collection of the required starting material according to an agreed blood-collection and transport plan.
Cell Processing
Isolation or enrichment of suitable mononuclear cells and monocytes.
Differentiation
Differentiation of suitable precursor cells into dendritic cells under defined culture conditions.
Antigen Loading
Exposure to the intended tumour-associated antigen source, for example tumour material, peptides, proteins or RNA-based information.
Maturation
Development of a functional profile intended to support antigen presentation, migration and T-cell stimulation.
Quality control
Product-specific testing including cell count, viability, identity, purity and microbiological safety.
Release
Documented release, preparation for administration and controlled handover to the treating facility.
Administration schedule
In a commonly used schedule, four administrations are initially planned at approximately monthly intervals. Depending on tumour type, disease course, study protocol and medical assessment, the schedule may be extended. For some tumour diseases, such as glioblastoma, longer administration series have also been described in studies.
- After laboratory release, the intended doses are delivered under controlled conditions in a frozen state.
- The first dose is thawed before administration in accordance with the laboratory instructions.
- The remaining doses are stored frozen immediately after receipt under the temperature conditions specified by the laboratory.
- Before each scheduled administration, the respective dose is thawed according to the laboratory instructions.
- Batch, storage conditions, thawing time, administration and any reactions are documented by the medical staff.
Treatment duration and follow-up monitoring
An individualised treatment course may extend over approximately five to six months. The number and spacing of administrations depend on the tumour disease, blood values, treatment dynamics and the overall medical plan.
Immune Status Check
A measurement before treatment describes the immunological baseline. A second measurement enables structured follow-up monitoring.
Read more about immune status →Tumour count and tumour dynamics
Baseline, interim and final measurements allow a dynamic assessment instead of relying on an isolated single value.
Read more about tumour dynamics →What happens if blood values are unfavourable?
If the blood count, immune-cell distribution, infection status or organ function do not provide suitable conditions for cell collection, blood collection may be postponed. Possible causes are reviewed first, such as recent chemotherapy, steroid treatment, infection, inflammation or a deficiency state.
After medical stabilisation, the blood count and, where appropriate, immune status can be reassessed. Supportive infusion or injection measures should only be used following an individual medical assessment.
Overall conceptPossible combination therapies
Dendritic cell therapy is often considered as part of a multimodal treatment concept rather than in isolation. The suitability of a combination depends substantially on tumour type, stage, biomarkers, disease dynamics and treatments already in progress.
| Treatment measure | Possible relationship with DCT | Important points to assess |
|---|---|---|
| Surgery | Reduction of tumour mass and possible collection of tumour material. | Wound healing, timing, pathology and antigen source. |
| Chemotherapy | Tumour-cell breakdown may influence antigen release; at the same time, relevant immune-cell values may temporarily decrease. | Blood count, monocytes, lymphocytes, cycle interval and infection. |
| Radiotherapy | Local cell damage may alter immunological signals and antigen release. | Radiation field, dose, inflammatory response and sequence. |
| Checkpoint Inhibitors | Activated T cells and reduction of inhibitory signals may have complementary effects. | Autoimmune risks, organ values, approved indication and timing. |
| Hormone and targeted therapy | Tumour control may be combined with an accompanying immunological strategy. | Agent, biomarkers, adverse effects and treatment outcome. |
| Hyperthermia and other approaches | Cellular stress and immunological changes are being investigated as possible complementary mechanisms. | Tumour type, procedure, cardiovascular burden and scientific evidence. |
General studies and research
Studies of dendritic-cell procedures differ substantially in terms of cell product, antigen source, maturation, route of administration, tumour type and clinical endpoint. Results from one specific procedure therefore cannot automatically be transferred to other products.
NCI: Cancer Treatment Vaccines
Open official NCI information →NCI: Therapeutic autologous dendritic cells
Open clinical trials →Trial watch: anticancer vaccination with dendritic cells
Open PubMed →The role of dendritic cells in cancer immunity
Open PubMed →For which tumour types can an assessment be performed?
A structured assessment can be performed, among other indications, for glioblastoma, lung cancer, breast cancer, colorectal cancer, prostate cancer, pancreatic cancer, melanoma, ovarian cancer, gastric cancer and bladder cancer. The assessment differs fundamentally according to tumour type, disease stage and previous treatment measures.
Frequently asked questions about dendritic cell therapy
Is dendritic cell therapy a standard cancer treatment?
Not for every tumour type and not in every disease situation. Evidence, regulatory status and suitability need to be assessed for the specific cell product and the individual patient.
What does the treatment process usually involve?
Typical steps include review of medical records, diagnostics, blood collection, patient-specific cell manufacturing, quality control, release, applications and follow-up. The binding process is the individually defined medical and laboratory-specific protocol.
Can dendritic cell therapy be combined with chemotherapy or radiotherapy?
A combination may be considered depending on tumour type, blood count, immune status, medication and timing. A general recommendation is not possible.
What effect can be guaranteed?
Tumour regression, cure or a specific survival time cannot be guaranteed. The biological aim of inducing an immune response is not proof of individual clinical effectiveness.
Which documents are useful for an initial orientation?
Current medical reports, pathology, imaging, blood results, previous treatments and the current medication list are helpful. Medical documents should only be sent through the designated secure submission route.