What is Vaccine prep therapy?

RGCC’s Vaccine prep therapy uses tumor cell antigens that are produced from the patients’ isolated circulating tumor cells. Tumor cells from each patient potentially carry gene mutations encoding for unique TAAs that are important in stimulating
effective and long-lasting anti-tumor responses in the patient. 

Tumor cells express a whole array of Tumor Associated Antigens (TAA) that are both characterized and uncharacterized, and this rich source of antigens contains epitopes of both CD8+ cytotoxic T cells (CTLs) and CD4+ T helper cells. This is important, as the parallel presentation of both MHC Class I and II restricted antigens would help generate a stronger overall anti-tumor response and long term CD8+ T cell memory via CD4+ T helper cells. 

Whole tumor cells are a very simple approach and can potentially be administered directly, without the need for dendritic cells (DC). Live tumor cells, however, are poorly immunogenic and shown to secrete soluble factors, such as vascular
endothelial growth factor (VEGF) which can suppress the DC’s dierentiation and maturation. 

A widely used and straightforward method of tumor cell preparation already used in clinical trials is necrotic whole tumor cell lysate. Whole tumor cells can be made necrotic by several methods. These methods generate cell material that contains a crude mixture of all kinds of cellular components including fragments of the destroyed cellular membrane, intracellular organelles such as mitochondria, and cellular RNA and DNA. Necrotic tumor cells have been shown to induce partial maturation in DC without further addition of maturation stimuli, probably due to the abundance of heat shock proteins which are released from dead cells after primary necrosis.

What kind of cancers can be treated with Vaccine prep therapy?

• Solid tumor only

What kind of cancers will not respond to the Vaccine prep therapy?

• Hematologic cancers
• CNS cancers
• Testicular cancers
• Compartmentalized cancers (isolated in an organ ex: brain)

At what cancer stage should a patient consider Vaccine prep therapy?

Since this therapy performs best with strict conditions, specifically a patient with an intact immune system, a patient can consider Vaccine prep therapy when:

• Patient is in early stage of the disease process
• Patient has not undergone chemotherapy or radiation
• Patient is not on any immune suppression therapies

Are there any contraindications to Vaccine prep therapy?

• Advanced stage of disease
• 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.
• Immune Suppression Medication – the patient will need to wait at least 14 days
• Recent blood transfusions – the patient will need to wait 120 days
• Cachexia
• Pregnancy or breastfeeding
• 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 <2500 (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 (any %) are not eligible
• Children under the age of 18 are not eligible
• Active Autoimmune Disease. Patients are not eligible
• Radioactive Seeds: Patients are not eligible due to the prolonged and undetermined time of the radiation exposure
• Gamma Delta T Cell Therapy (GDTC): Patients are not eligible due to the potential interaction with the therapy

Is Vaccine prep therapy safe?

• Yes. The VACCINE PREP is a type of therapy that uses antigens from the isolated CTCs in the patient’s own blood. It is a personalized therapy and as such it comes with all the safety advantages of a personalized therapy.
• There have been over 1150 clinical trials thus far on their use

What happens if the patient’s immune system doesn’t respond to the Vaccine prep therapy?

• If the patient’s immune system does not respond to the Vaccine Prep, then it’s recommended to change the therapeutic strategy.

What is the administration schedule of the Vaccine prep therapy?

• The therapy is given over a total of nine (9) weeks
• Doses 1, 2 and 3 – are given on weeks 1, 2 and 3 – (8 days apart - consecutively)
• No injections for three consecutive weeks (weeks 4,5, and 6) to allow for the building of the immune response
• Doses 4, 5 and 6 – are given on weeks 7, 8 and 9 – (8 days apart – consecutively) for completion of the cycle)
• Follow up Oncotrace and Immune Frame is on Day 72 

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.

How often can the Vaccine prep therapy be given?

• The therapy can be re-ordered and repeated at three (3) month intervals after the date of the last dose administered
• You will need to send in a new blood sample of 25 ml for any repeat of the VACCINE PREP
  

What is included in the Vaccine prep therapy package and what is the cost?

• Package Price: 3600 Euro
• Package Includes:
  • All six (6) doses Vaccine prep therapy
  • 1 Follow up Immune Frame after the sixth dose (Day 72)
  • 1 Follow up Oncotrace after the six dose (Day 72)
• Package DOES NOT include:
  • Initial (baseline) Immune Frame
  • Initial (baseline) Oncotrace

What are the mandatory prerequisite tests required to establish baseline for Vaccine prep therapy?

• Pre-Immune Frame (Baseline/Initial for status of immune system)
• Oncotrace – (Baseline CTC) Note: If drawing Immune frame and Oncotrace at the same time – one 30 ml vial is sufficient)

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

What are the mandatory follow up tests for Vaccine prep therapy?

• Mandatory Follow-Up Testing: DAY 72
  • Immune Frame – 21 days after the 6th dose of the therapy or 72 days from Dose 1
  • Oncotrace – 21 days after the 6th dose of the therapy or 72 days from Dose 1

Important: If the administration schedule was altered at all, the follow up is 21 after days after dose 6.

Important: 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 repeat of the therapy or a change in therapy becomes necessary. These tests are optional and not included in the original therapy package.

How do I place an included follow up test order?

• The Day 72 follow up tests are not ordered in the doctor’s portal
• These are ordered via a “letterhead order.”
• Simply write on your clinic’s letterhead the patient's name and that you are ordering the Oncotrace and Immune Frame for the specific follow up
• Include the letterhead order with the patient’s blood sample.
• Email letterhead order to info@rgcc-international-northamerica.com

Note: Additional information on Letterhead Orders is in the Orientation Guide on page 24. You can download this document from the Resources section of the Doctor’s Portal.

How much blood is needed for Vaccine prep therapy?

• Initial Immune Frame (Baseline test) (Draw 15-25 ml of blood) 1 vial
• Initial Oncotrace (Baseline test) (Draw 15 ml) 1 vial
• All six doses of the Vaccine prep therapy (Draw 25-30 ml) 1 vial
• Follow up Immune Frame (Draw 15-25 ml of blood) 1 vial
• Follow up Oncotrace (Draw 15-25 ml of blood) 1 vial

Note: If drawing Immune Frame, Oncotrace and Vaccine Prep at the same time - two vials of 30 ml each is sufficient)

What pre-medications are required for Vaccine prep therapy?

• Mandatory: 4 mg dexamethasone IV in a 20-50 ml rapid drip saline solution or slow bolus push.

What needs to be avoided PRIOR to the pre-Immune Frame and the actual Vaccine prep therapy?

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
• 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
• Scans with 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 the bloodstream.
• Hyperthermia (generalized/systemic): no waiting
• Hyperbaric Therapy: at least 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

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.

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

In deciding what might or might not interfere with the development of the memory cells, ask yourself 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 do 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 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 x 5)
• Checkpoint inhibitors (can be beneficial)
• Mild Hyperthermia (Infrared Sauna)
• SOT therapy (can be beneficial if given at least 14 days prior)

What needs to be avoided AFTER Vaccine prep therapy?

• The patient must stay off ALL cytotoxic, or free radical producing, and immune suppressing therapies for at least 21 days after the administration of the therapy.

Are there any possible adverse reactions with Vaccine prep therapy?

• Flu-like symptoms
• Fatigue
• Fever
• Injection site reaction (skin rash)
• *Uticaria (hives)

*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 Vaccine prep therapy?

The goal of therapy is to decrease the number of CTCs and for the follow up Immune Frame to show activation of the immune system.

1. Baseline: Patient is not eligible for therapy if the pre–Immune Frame shows:
   • High Tregs (CD25 + CTLA4) (Any % will interfere with memory cell development)
   • High TNF-a (over 5%)
2. Monitoring Progress: Follow up Immune Frame for Vaccine Prep is at Day 72.
   • Any rise of markers except for CD25, CTLA4 and TNF-a is an indication of activation
3. Final Outcome: Day 72 – 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)
4. Repeat or change in therapy strategy is necessary:
   • If the Immune Frame at Day 72 does not show the expected results as outlined above under Final Outcome.

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 Comprehensive Guide.

How to Administer Vaccine prep therapy

PRE-MEDS: Administer pre-medications prior to each IV dose of the Vaccine prep therapy

• Ready premedication of 4 mg dexamethasone in a 20-50 ml rapid drip saline solution or very slow bolus push)

First steps:

• The VACCINE PREP will come in a single (6) ml powder form. It is shelf stable at room temperature until it is reconstituted.
• The designation will be VACCINE PREP (Autologous Tumor Antigen)
• The name of the patient will not appear on the therapy vial. It will be a number and must be matched to the patient’s name on their paperwork
• Inspect the vial upon receipt. The vial should be a crystalized powder form without any signs of precipitation
• In case of any precipitation DO NOT ADMINISTER. Immediately notify RGCC by email at info@rgcc-international-northamerica.com and call 1-800-813-1372.
• In its original crystalized/powder form the VACCINE PREP can be stored at ambient room temperature and out of sunlight for 4 months (120 days) if necessary (but not recommended) or can be kept in the refrigerator.
• DO NOT FREEZE the therapy in its crystalized form

Important: You will need to have ordered from your medical supplier five (5) cryo vials to separate out the additional doses. These vials are no longer supplied by RGCC.

Therapy Administration:

Dose 1 – Week 1

• You will have received a single vial of 6 mL of the therapy in a powdered form
• Do not reconstitute the powder until you are ready to administer the first dose
• Administer the premedication of 4 mg dexamethasone
• Take the therapy vial and add 6 mL of sterile water to the vial
• Tilt it back and forth gently to mix the solution. This should be done several times and should take 1-2 minutes to completely dissolve the crystals and final product should be completely clear
• The therapy is now reconstituted
• Immediately after reconstitution draw out your first 1 mL dose with a syringe (AVOID fine needles - use an 18 – 19 G needle) and set aside
• The remaining reconstituted solution can be put into the freezer at -20 or -80 degrees or the recommended and preferred method is to split the remaining solution into five (5) separate cryo vials with 1 mL of the therapy in each vial and freeze them individually (this avoids the repeated thaw and refreeze cycle associated with using the original vial to all doses).
• Administer the first 1 mL vial intravenous as outlined below

How to administer Vaccine prep therapy:

• Administer the premedication of 4 mg dexamethasone
• Add the first 1 mL vial of the therapy to 100 ml saline bag
• Gently swirl/tilt the prepared solution a few times to mix well
• Infusion the therapy as a rapid drip IV
• Observe the patient for 30-45 minutes

Note: This is the only form of delivery recommended now since it has been found to be the most eective over larger areas with less concentration (large concentrations are not necessary to activate the antigen presenting cells).

Important: NEVER INJECT DIRECTLY INTO A TUMOR!!

Doses 2 & Dose 3 (week 2 and 3)

• Administer the pre medication of 4 mg dexamethasone
• Remove a 1 mL cryo vial from the freezer
• Bring to ambient temperature by holding in your hand for a few minutes - DO NOT HEAT VIAL
• Draw out the 1 mL from the vial
• Add the 1 mL vial to 100 ml saline bag
• Gently swirl/tilt the prepared solution a few times to mix well
• Infusion the therapy as a rapid drip IV
• Observe the patient for 30-45 minutes

Weeks 4, 5 and 6

• The patient has three weeks of no injections to allow for the immunity to build

Doses: 4, 5 and 6 (weeks 7,8 and 9)

• Administer the same as Doses 2 and 3