What is VAXO-Q-RE Therapy?

• VAXO-Q-RE is best described as an Autologous Adoptive Cellular Therapy. It consists of the basic players of innate and adaptive immunity, i.e., macrophages and Natural Killer cells (innate immune cells) and activated Dendritic Cells, T cells and antibody producing plasma cells (adaptive
  immune cells). Innate immune cells are ready to fight any pathogen or cancer cell in an antigen independent manner, while T cells and B cells require pre- activation with antigenic peptides. Activation of adaptive immune cells is performed with dendritic cells, a type of antigen presenting cells (APC). All these cells can be generated from a patient’s blood and then be infused back to the patient.

How does VAXO-Q-RE work?

• Action role of immune cells: Macrophages and Natural Killer cells can recognize and kill foreign pathogens and cancer cells. Macrophages are phagocytic cells and Natural Killer cells both, can eliminate cancer cells in an MHC-independent manner. Cytotoxic T-cells (CTLs) are activated against specific antigens by dendritic cells and have the ability to target and kill cancer cells expressing the specific antigen. Antibodies produced by plasma cells, tag cancer cells and help their recognition by phagocytes or complement proteins leading to their subsequent destruction.
• RGCC’s laboratories uses a patient’s isolated peripheral blood mononuclear cells as a source for the in vitro production of VAXO-Q-RE. Macrophages and Natural Killer cells are selected and expanded in large numbers. Monocytes are used as a source for the production of dendritic cells (DCs). DCs are then pulsed with synthesized peptides designed specifically to mount an immune response against tumor proteins. These peptides are selected carefully so as to activate both T-lymphocytes (CTLs) as well as antibody producing cells aiming at long term memory cells and overall protection. VAXO-Q-RE is composed of three doses, containing innate immune cells (macrophages and Natural Killer cells) and adaptive immune cells (CTLs and antibody producing cells).

What is the goal of VAXO-Q-RE?

• Boost Natural Immune System defence against the patient’s cancer
• Activation of immune cells with patient’s tumor antigens

What kind of cancers can be treated with VAXO-Q-RE?

• Theoretically all blood and solid tumor cancers can be treated if circulating tumor cells can be found in the blood. However, the therapy is primarily aimed toward solid tumors.

What kind of cancers will not respond to VAXO-Q-RE?

• Central Nervous System Cancers (due to the blood brain barrier)

At what cancer stage should a patient consider VAXO-Q-RE?

• A patient must be staged at a minimum of grade 2B
• A patient can consider VAXO-Q-RE when all other options have been exhausted as long as the disease is stable and the patient is not on any chemotherapy or radiation therapy concurrently.

Are there any contraindications to VAXO-Q-RE?

• Currently on chemotherapy or radiation
• Recent radiation or chemotherapy - the patient will need to wait a minimum of three (3) weeks.
  • The 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
• Cachexia
• Pregnancy or breast feeding
• 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
• High TNF-a on the pre–Immune Frame (should be under 5%)
• Tregs on the pre-Immune Frame (should be under 5%)
• Children under the age of 18 are not eligible
• Active Autoimmune Disease. Patients are not eligible for the therapy
• Radioactive Seeds: Patients are not eligible for therapy due to the prolonged and undetermined time of the radiation exposure.
• Gamma Delta T Cell Therapy (GDTC): Patients are not eligible for therapy due to the potential interaction with the VAXO-Q-RE therapy.

Why can’t VAXO-Q-RE be done on children?

VAXO-Q-RE has 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 VAXO-Q-RE safe?

• VAXO-Q-RE is an Autologous Adoptive Cellular Therapy and is generally a very safe procedure.

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

• This therapy is creating the required immune response ex vivo, so there will be a response. 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 and blood draw timeline for the VAXO-Q-RE?

• Timeline is: one dose every two weeks for three total doses and two sets of follow up tests:
  • Pre-tests are drawn and ordered: (Oncotrace and Immune Frame)
  • Therapy is ordered and blood is drawn: (The time frame from initial order to receipt of the therapy is approx. 21 days)
    • Day 0 – 1st dose administered (Macrophages and NK cells)
    • Day 15 – 2nd dose administered (APCs, CTLs and plasma cells) - 2 weeks after Dose 1
    • Day 30 – 3rd dose administered (APCs, CTLs and plasma cells or Macrophages and NK cells or a mixture of what the patient needs as determined by RGCC)
    • Day 120 – Mandatory Follow up Immune Frame and Oncotrace - Included in package
    • Day 210 – Mandatory Follow up Immune Frame and Oncotrace - Included in package
      

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.
• It is highly recommended to infuse on the day of delivery (Day 6 = Tuesday), if that is not possible then the next morning. 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 no longer be viable and should not be administered unless confirmed by the lab that they are still viable.

Is the administration timeline flexible for VAXO-Q-RE?

• 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 at day 120* are calculated at 90 days after Dose three (3) and then another 90 days after that for day 210* follow up tests.
• If a booster is given based on day 120 results, the day 210 follow up tests will move to 120 days post booster administration date. If a booster is given based on day 210 results, there will be no further follow up tests included in the package price.

What is included in the VAXO-Q-RE package?

• Therapy Package from RGCC Includes:
  • All three doses of the VAXO-Q-RE Therapy
  • 2 Follow up Immune Frames – Day 120 and Day 210
  • 2 Follow up Oncotrace Tests – Day 120 and Day 210
• Package DOES NOT include:
  • Initial (baseline) Immune Frame
  • Additional follow up Immune Frames (past the Day 120 and Day 210 ones)

What are the mandatory pre-requisite tests to establish a baseline and eligibility for VAXO-Q-RE?

• Immune Frame (initial/baseline immune status) - not included in package
• Oncotrace (Baseline CTC) – not included in package
• It is highly recommended to evaluate the baseline Oncotrace and the initial Immune Frame prior to ordering the therapy to verify the patient’s eligibility. 30 ml of blood (1 vial) is sufficient for both tests if ordered at the same time.

What is the mandatory follow up tests for VAXO-Q-RE?

• Mandatory Follow up Testing: Day 120 (90 days from Dose 3)
• Mandatory Follow up Testing Day 210 (90 days from Day 120 testing)
• Immune Frame for verification of immune response
• Oncotrace for the follow up cell (CTC) count

The lab will evaluate these results and if patient is not at expected levels, a second round of VAXO-Q-RE may be recommended.

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.

Important relative to boosters:

• If a booster is given based on day 120 results, the day 210 follow up tests will move to 120 days post booster administration date.
• If a booster is given based on day 210 results, there will be no further follow up tests included in the package price.

How much blood is required for VAXO-Q-RE?

• Initial Immune Frame (Baseline test) (15-25ml of blood)
• Oncotrace (initial CTC – baseline test) (15ml of blood)
• Dose 1, 2 and 3 of VAXO-Q-RE (120-140ml of blood)
• Follow up Immune Frame (15-25 ml of blood)
• Follow up Oncotrace (15ml of blood)

Note: if ordering the Oncotrace, Immune Frame and all the three doses of the therapy at the same time then 150 ml of blood (5 vials) will be sufficient.

Is there any data on outcomes with the VAXO-Q-RE?

The newest article that has been recently published regarding the VAXO-Q-RE therapy outcome can be viewed here: https://www.sciencedirect.com/science/article/pii/S0008874922001411

What needs to be avoided prior to the pre-Immune Frame and the actual VAXO-Q-RE?

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
• Hyperbaric Therapy: 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
• 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 prior to OR after 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 (can be beneficial if given prior)

What needs to be avoided after VAXO-Q-RE?

• In order to allow the memory cells to fully develop it is best that patient’s stay off ALL cytotoxic, or free radical producing, and immune suppressing therapies 120 days after the administration of the therapy.
• If 120 days is not possible due to advanced state of disease, the patient is able to resume:
• IV Vitamin C after 7 days
• Mistletoe after 7 days
• PEMF after 7 days
• Rife after 7 days
• Hyperbaric Oxygen Therapy after 7 days
• Ozone after 14 days
• **Other treatments or therapies after 21 days including cytotoxic
  therapies and off label medications

Note: Other substances must be evaluated on their half-life. Please ask your RGCC provider for
specific information.

Important: understand (doctor and patient) that the memory cells will be impacted and patient
may not obtain full benefit of the therapy.

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

Talk to your RGCC practitioner on what needs to be avoided in your particular case. In deciding what might or might not interfere with the development of the memory cells, it must be determined 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.

What pre-medications are required for VAXO-Q-RE?

PRE-MEDS: Administer pre-medications prior to each dose of the THERAPY.

• Mandatory: 4 mg Dexamethasone for does 2 and 3 only. Not used with Dose 1.
• Optional but highly recommended: IV H2 inhibitors: Famotidine, Cimetidine, or 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.
• 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.

Are there any possible adverse reactions with VAXO-Q-RE?

• Flu-like symptoms
• Fatigue
• Fever
• Injection site reaction (skin rash)
• *Uticaria (hives)
• Tumor Lysis Syndrome (TLS) with large volume of tumors
• Pain, swelling and inflammation at tumor site
• Tumor Lysis Syndrome (TLS) with large volume of tumors
• Pain, swelling and inflammation at tumor site

*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 is the expected outcome with VAXO-Q-RE?

Expected outcome would be indicators (based on statistical analysis of CTCs and immune status ie CD 80/CD 86/ CD 28 numbers on the follow up Immune Frames), as well as on clinical evaluation and Karnofsky Index) that an up-regulation of immunity was achieved.

What are the expected values on the Immune Frame after completion of the VAXO-Q-RE?

Sample Day 120 – 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 is ok)

Sample Day 210 (long term immunity is established) – Expected results:

• T&B cells (central) should be steadily present and
• CD 80 and CD 86 should be over 22%
• CD 28 on B and T lineage should be above 1%
• If memory cells are not well established on Day 120 or Day 210 then a booster or a 2nd round of VAXO-Q-RE should be administered.
• There is only the option of one single booster per round of therapy so choose wisely.

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.

How is it determined if the patient needs a Booster or a repeat of the therapy? 

Your RGCC practitioner will evaluate the follow up Oncotrace and Immune Frame results and if they determine that optimal results were not obtained, then they are responsible for submitting a request for evaluation to the lab.

• The scientists at the lab will evaluate all the relevant data and will advise whether a booster or a repeat of the VAXO-Q-RE is recommended.
• Patients are only eligible for one booster per paid round of the therapy.
• A booster request must be submitted within 30 days of the Day 120 follow up Immune Frame or within 60 days of the Day 210 Immune Frame.
• Note: If booster is given after day 120 results, there will not be a day 210. Instead, the follow up tests will be 120 days POST booster.
• If booster is given after day 210 results, no further follow up tests will be included in the package price.