What are DENDRITIC CELLS?

• Dendritic Cells (DCs) are known as antigen presenting cells. They are special key regulators of the Immune system capable of activating the T-Cells and stimulating the growth and differentiation of B-Cells. Dendritic cells identify specific protein markers known as peptides on the surface of foreign or invading cells. DCs then present these peptide markers to other cells in the immune system so that they can seek out cells that carry this specific marker and destroy them.

What is DENDRITIC CELL THERAPY?

• Dendritic Cell Therapy harnesses the action of Dendritic Cells by identifying specific antigens on the cancer cells circulating in the blood of an individual, allowing the immune system to seek out the cancer cells to destroy them. It also stimulates memory cells providing long lasting immunity.
• Dendritic Cell Therapy is not a genetic therapy.
• Dendritic Cell Therapy does not involve the use of genotoxic (chemo) drugs.

How is the DENDRITIC CELL THERAPY made?

• Individualized dendritic therapies are created by isolating the Dendritic Cells and Circulating Tumor Cells (CTCs) from a fresh blood sample of a cancer patient. The CTCs are analysed to identify the most frequently expressed protein (epitope) on the surface of these cells. This cancer protein is then imprinted on to the dendritic cells. The dendritic cell population is then augmented into millions, and the final preparation is created for administration to the patient.

What is the goal of DENDRITIC CELL THERAPY?

• The goal of the Dendritic Cell Therapy is to prime dendritic cells to teach T cells and B cells to recognize the cancer epitopes. Eventually, the CD28 T cells form memory to teach new dendritic cells to execute the same process as the initial. If the DENDRITIC CELL THERAPY is effective, it will provide the patient with long-term immunity against the cancer cells.
• Immune Frame testing is done prior to Dendritic Cell Therapy administration to establish the baseline immune system status and repeated as follow-up testing to monitor the immune system’s response. Dendritic Cell Therapy “boosters” can be made in the future for the patient if the dendritic cells or the CD28 T cells lose potency or memory.

What kind of cancers can be treated with DENDRITIC CELL THERAPY?

• Solid tumors only

What kind of cancers will not respond to DENDRITIC CELL THERAPY?

• Hematologic malignancies
• Testicular Cancer
• Compartmentalized cancers (isolated in an organ ex: brain)
• CNS cancers – Dendritic cells do not usually pass through the blood brain barrier to reach the target. Therefore, CNS cancers have to be biopsied in order to create the therapy and consequently are less likely to work as well as it does with other types of cancer.

At what cancer stage should a patient consider DENDRITIC CELL THERAPY?

• Any stage can be considered if the cancer is stable and the patient is not on any concurrent chemotherapy, radiation or immune suppressive therapies.
• Also appropriate for the patient that is currently in remission and seeking to reduce the likelihood of a cancer reoccurrence.

Are there any contraindications to DENDRITIC CELL THERAPY?

• Current treatment with chemotherapy or radiation.
• Recent radiation or chemotherapy - the patient will need to wait a minimum of three (3) weeks.
  • This therapy requires a full useable immune system to be effective so this time frame is only an estimate and may be longer depending on the status of the patient, and their immune system’s ability to restore itself. Careful evaluation needs to be done by the healthcare provider before recommending this therapy to insure optimal response.
• Recent blood transfusions – the patient will need to wait 120 days
• Immune Suppression Medication must wait at least 14 days
• Active Autoimmune Disease: Patients are not eligible for the therapy
• Cachexia
• Pregnancy or breast feeding
• Children (under the age of 18)
• Active infections – (includes active Lyme and coinfections)
  • Indicators:
    • WBC >10,000
    • Lymph > 20%
    • CRP >3.0
• High inflammation:
  • Indicators:
    • CRP>3.0)
    • Sed Rate >29 mm
    • AGP- a1-acid glycoprotein >110
    • ANC <500 (indicator of immune insufficiency)
    • Hemoglobin <8.5
• Tregs (CD25 + CTLA4) are present on the pre-Immune Frame (any %)
• High TNF-a on the pre–Immune Frame (should be under 5%)
• Radioactive Seeds: Patients are permanently not eligible for the therapy
• Gamma Delta T Cell Therapy (GDTC): Patients are permanently not eligible for the therapy

Why can’t DENDRITIC CELL THERAPY be done on children?

Dendritic Cells have not been evaluated in children. They have an immature immune system and we do not know the effect the immune system and development of self-tolerance. Additionally, children have an active thymus gland and their immune system is under development. Therefore, it is not
recommended.

Is DENDRITIC CELL THERAPY safe?

• Multiple studies, including human trials and clinical experience have established the DENDRITIC CELL THERAPY as generally safe.
• There are over 800 clinical trials on DC’s with over 200 active trials currently underway.

Are there studies on Dendritic Cell Therapy?

• https://www.intechopen.com/books/biology-of-myelomonocytic-cells/dendritic-cells-location-function-and-clinical-implications
• https://www.nature.com/subjects/dendritic-cells
• https://pubmed.ncbi.nlm.nih.gov/31810551/
• https:/www.ncbi.nlm.nih.gov/pubmed/10073291

What happens if the patient’s immune system doesn’t respond?

If there is not a successful response by the patient’s immune system by the end of the third dose (based on follow up Immune Frame results) you can either start a new DC therapy cycle with a different antigen OR change the therapeutic strategy altogether. The particular level of response will be dependent on the status and health of the patient as well as if the patient adhered to the pre and post therapy guidelines. Resuming immune inhibiting /cytotoxic treatments will impact the ultimate outcome of therapy since they directly impact the memory cells.

What is the administration schedule of DENDRITIC CELL THERAPY?

• One dose every 21 days for three total doses and two follow up tests:
  • Therapy Infusions are on Days 0, 21 and 42
  • Follow up Immune Frame and Oncotrace are drawn on Day 63
    

Important:

• Remember that day “0” is counted as Day 1 in terms of counting for dose infusions as well as for mandatory follow up tests.
• These are live cells and need to be kept cold. Your provider should be tracking the therapy to ensure that it will be arriving during business hours.
• It is highly recommended to infuse on the day of delivery (Day 6 = Tuesday) and if that is not possible then the next morning (Day 7 = Wednesday). Do not intentionally wait to infuse.
• Shipment from lab is on a Thursday (Day 1) administration must occur by Wednesday (Day 7) of the following week at the absolute latest.
• After Thursday (Day 8) the cells may not be viable and should not be administered unless confirmed by the lab that they are still viable.

Is the administration timeline flexible for DENDRITIC CELL THERAPY?

• It is recommended to follow the recommended administration schedule to ensure that the patient receives the highest viability/effect.
• Both doctors and patients need to schedule the administration of all three doses in advance to receiving dose one (1) in order to avoid any delays with the additional two doses that will be upcoming.
• Should there be an unexpected delay, the therapy can be requested to be shipped and administered up to one week late without loss of efficacy. Past this window, the therapy loses its potency and the patient will not receive the full benefit. If therapy is already shipped this option is
  no longer available.
• If the administration schedule was altered at all, then the follow up tests are to be drawn 21 days after Dose 3 (considering the delay was within reasonable limits).

What is included in the DENDRITIC CELL THERAPY package and what is the cost?

• Package Price: Ask your RGCC practitioner
• Package Includes:
  • All three (3) doses of the Dendritic Cell Therapy
  • 1 Follow up Immune Frame after the third dose (Day 63)
  • 1 Follow up Oncotrace after the third dose (Day 63)
• Package DOES NOT include:
  • Initial (baseline) Immune Frame and Oncotrace
  • Additional follow up Immune Frames (past the Day 63 one)

What are the mandatory pre-requisite tests required to establish baseline for DENDRITIC CELL THERAPY?

• Initial (Pre) Immune Frame – Initial/Baseline immune system status
• Initial Oncotrace – (Baseline CTC)

Reminder: the initial baseline tests are not included in the cost of the actual therapy)

How much blood is required for DENDRITIC CELL THERAPY?

• Initial Immune Frame (Baseline test) (Requires 15-25 mL of blood) 1 vial
• Initial Oncotrace (Baseline test) (Requires 15ml) 1 vial
• Dose 1, 2, and 3 of DENDRITIC CELL THERAPY (Requires 70-80 mL of blood) 3 vials

NOTE: if ordering the Oncotrace, Immune Frame and the three doses of the therapy at the same time then 80ml of blood (3 vials) will be sufficient

It is highly recommended that the Immune Frame be evaluated prior to ordering the therapy. In that case, 30ml of blood (1 vial) is sufficient for both baseline tests if ordered at the same time.

What are the mandatory follow up tests for DENDRITIC CELL THERAPY?

• Mandatory Follow-Up Testing: Day 63 (which is 63 days from Dose 3)
• Immune Frame for verification of immune response
• Oncotrace for the follow up cell (CTC) count

Note: It is highly recommended to run a follow-up Immune Frame test every 6 months for at least 2 years to monitor CD80, CD86 and CD28 levels to determine if a booster becomes necessary. These tests are optional and not included in the original therapy package.

What pre-medications are required for DENDRITIC CELL THERAPY?

• Mandatory: 4 mg dexamethasone I.V. in a 20-50 ml rapid drip saline solution or slow bolus push.
• Optional but highly recommended: IV H2 inhibitors: Famotidine, Cimetidine, Nizatidine given at least 60 min before IV. The reason for the H2 blocker is to decrease any chance of headache, nausea, vomiting, and diarrhea. This is rare but very unsettling if it happens to your patient.
• Optional: Paracetamol (Acetaminophen), PO 500 mg, three time per day for up to three days starting an hour before the application, in order to counteract headache that could develop.

What needs to be avoided prior to the pre-Immune Frame and the actual DENDRITIC CELL THERAPY administration?

Pre-Therapy Administration: The patient must be off ALL cytotoxic and free radical producing therapies. If drawing for cellular therapies, the patient must be off ALL immune suppressing therapies as well.

• Natural Substances (IV): cytotoxic substances like Vitamin C or Ozone at least 14 days.
• Natural Substances (oral supplements): Class 1 or 3 cytotoxic substances (per patient’s Onconomics Plus results) at least 14 days.
• Off Label Medications: Ivermectin-FenBen-Itraconazole: 21 days
• Methylene Blue: at least 14 days
• Chemotherapy (non-platinum derivative): at least 14 days.
• Chemotherapy (platinum derivative): at least 21 days.
• MOAB or SMW drugs for at least 14 days.
• Blood Transfusions: at least 120 days.
• Radiation: at least 14 days.
• Contrast: at least 14 days.
• Surgery (simple/routine): at least 7-10 days.
• Surgery (brain or extensive): minimum of 30 days based on time of recovery. Could be longer if slow recovery or if the person had some type of adverse reaction. Must be evaluated on a case-by-case basis.
• Fever: at least 14 days.
• Hyperthermia (local/concentrated/microwave ablation): at least 30 days due to increase in cellular debris released into blood stream.
• Hyperthermia (generalized/systemic): no waiting.
• Hyperbaric Therapy: 14 days
• Cryoablation: no waiting.
• Immune Suppression Medication (All pre-Cellular Therapies – VAXO-Q-RE, Vaccine Prep, Dendritic Cells, DendroCov): at least 14 days.
• Mistletoe: 14 days
• Radioactive Seeds: Patients are not eligible for therapies due to the prolonged and undetermined time of the radiation exposure.
• Gamma Delta T Cell Therapy (GDTC): Patients are not eligible for therapies due to the potential interaction with RGCC therapies.

Note: The purpose of these guidelines is to ensure the highest level of effectiveness of each therapy by removing treatments that interfere with and/or diminish the effectiveness of that therapy. Adherence to these guidelines will improve therapy effectiveness and patient outcomes. Reason: The breakdown of the CTC caused by these substances creates debris that could interfere with the development of the memory cells. Allowing time for the body to clear the debris will increase the effectiveness of the therapy.

What does not need to be avoided for this therapy?

• Hormone Suppression Therapy (applies to most but not all since there are exceptions ex: Verzenio requires 3 days based on ½ life)
• Checkpoint inhibitors can be beneficial)
• Mild Hyperthermia (Infrared Sauna)
• Hyperbaric Therapy
• SOT therapy (actually beneficial to DC therapy if given at least 14 days prior)

What needs to be avoided after DENDRITIC CELL THERAPY?

• The patient must stay off ALL cytotoxic, or free radical producing, and immune suppressing therapies 21 days after the administration of the therapy.
• Avoid contracting Parvovirus B19. This will most likely completely destroy the cellular immunity that the therapy created.

The above is not an exhaustive list of problematic substances, so how can you decide what might interfere with the development of memory cells?

Ask your RGCC provider what you need to avoid. In deciding what might or might not interfere with the development of the memory cells, it depends on if the product has a direct or indirect effect on the CTC (in either being directly cytotoxic or in the generation of free radicals). Those are the problem substances since they create inflammation and debris in the blood sample (the scientists call it noise). Example: Artemisinin breaks down DNA so it' works directly as a cytotoxin so it must be avoided. So does substances like Ivermectin, Ozone, Colloidal Silver, and Curcumin.

However, substances that work indirectly through the metabolism of cells (starving cancer) like Salicinium or Metformin only need to be avoided for 7 days after the administration of the therapy.

Additionally, substances like Flavonoids (ALL - including Quercetin and Resveratrol) and products like modified citrus pectin also work indirectly so they also only need to be avoided for the 7 days after administration of the therapy.

Are there any possible adverse reactions with DENDRITIC CELL THERAPY?

• Flu-like symptoms
• Fatigue
• Fever
• Injection site reaction (skin rash)
• *Uticaria (hives)
• Tumor Lysis Syndrome (TLS) with large volume of tumors
• Pain at surgical sites
• Increase in systolic blood pressure (usually 10-20 mm)

*Note: There has never been any reported severe life-threatening anaphylactic reaction from this
procedure. However, there is no guarantee that this will not happen, however rare it may be.

What are the expected results after DENDRITIC CELL THERAPY?

The end result of Dendritic Cell therapy is the decrease of CTCs and the follow up Immune Frame is showing the activation of immune system.

Baseline: Patient is not eligible for Dendritic Cell therapy if the pre-Immune Frame shows:

• High Tregs (CD25 + CTLA4) (Any %)
• High TNF-a (over 5%)

Monitoring Progress: Follow up Immune Frame for Dendritic Cells is at Day 63

• Any rise of markers except for CD25, CTLA4 and TNF-a is an indication of activation

Final Outcome: Day 63 – Immune Frame expected results:

• T&B cells should be steadily present
• CD 80 should be over 15%
• CD 86 should be over 10%
• CD 28 – B & T line should be above 0 (even barely ok)

Booster is necessary:

If the Immune Frame at Day 63 does not show the expected results as outlined above under Final Outcome.

What is the ultimate goal on the Immune Frame post DENDRITIC CELL THERAPY?

The ultimate long term goal is to develop a long-term immune response:

• >22 on both CD80 & CD86 memory cells
• >1.0 on CD28 memory cells

Important: This goal may not be obtained until the optional 6 month follow up Immune Frame.

This is done by increasing cell-mediated immunity and humoral immunity:

• Increasing INF-γ (interferon gamma)
• Increasing IL-2 (Interleukin 2)
• Increasing IL-4 (Interleukin 4)
• Increasing IL-6 (Interleukin 6)

This is done by decreasing the inflammation markers (the lower the negative the better):

• Lowering high TNF-a (Tumor Necrosis Factor alpha)
• Lowering high Tregs (T regulatory cells) CD25 and CTLA4

Is there anything that can be done to help obtain optimal results on the follow up Immune Frame?

Yes, you can recommend various nutrients to help improve the results on the Immune Frame. Please see our Immune Frame Patient Guide.

What is the new Booster policy for the DENDRITIC CELL THERAPY?

• If Day 63 Immune Frame results were not on target (per guidelines) the lab first recommends you consider a change in therapy (SOT, DC’s with a new epitope target, or conventional treatment).
• If a booster is desired, then a repeat of the Immune Frame (not included in package) must be repeated on Day 210 (plus/minus one week).
• If the results on Day 210 (plus/minus one week) still do not show the targeted numbers (per guidelines) then a booster can be requested.
• Boosters will not be approved prior to the Day 210 (plus/minus one week) Immune Frame results being posted.
• The booster request must be made in writing within 15 Days from the Day 210 Immune Frame results.
• The one time, one dose booster will be for the same epitope target of the original therapy
• Patient must not have undergone other cytotoxic therapies (radiation or chemotherapy)
• Patient must not have undergone other conventional immune therapies

When is a new DENDRITIC CELL THERAPY order required instead of a booster?

• It has been over 15 days from Day 210 Immune Frame.
• Memory cells have started dropping (to know this information patient will require an optional follow up Immune Frame between Day 63 and Day 210). Important: Optional Immune frames are not included in the package price of the therapy.
• Patient has undergone conventional cytotoxic or immune therapy since receiving the original DC therapy (this will automatically require a retargeting and even if within the booster timeline it will not be considered a booster).
• Important: a new Dendritic Cell Therapy is subject to the current pricing.