Update on April 2016: I do not see this option as a top option anymore given that I heard many actually starting to progress after starting this therapy. It is not only one person but several so a pattern starts to occur. Note that DC is typically given with New Castle Disease Virus – so I am not sure if NDV or DC leads to progression.
Dendritic cells (DC) therapy (in combination with anti PD1) is one of the most interesting cancer therapy. DC vaccine alone costs about 4500 euro for one vaccine and is available at various clinics in Europe and US. One of the best clinic working with Dendritic cells is that of dr. Nesselhut in Germany (for contact details see clinics section). They have a relatively large research lab supported by the German government. They are also collaborating with dr. Raymond Chang in USA (New York) so that their treatment is accessible in US as well. (Here is an introduction from dr. Raymond Chang on DCs.). Dr. Nesselhut clinic claims great results with DC and even more when combining with New Castle Disease virus andwith low dose anti PD1 (e.g. Nivolumab).
RGCC is also offering DCs through the clinics they are working with. If you like to investigate what are the options you can contact RGCC and ask what are the clinics near you that may offer their DC vaccine.
Dendritic cells: Monocytes are taken from the patient by means of leukapheresis (less desirable procedure for those with low immune system) or simple blood withdrawal, so that extra dendritic cells can be cultivated outside the body. Those dendritic cells are “educated” to recognize tumors (primed with tumor sample from patient or peptides and/or viruses such as New Castle) and returned to the patient. It is typically indicated to have multiple treatment of this type and it may be combined with theNew Castle Disease virus (NDV) administration. In this case NDV will be used to prime DCs. NDV is first introduced into the body and will end up localized in the tumors only, since the tumors do not have the capability to generate interferon and kill the virus. After some hours DC vaccine is administrated with the DCs previously primed to recognize NDV so that they will end up targeting thetumors. This is the technique used by dr. Nesselhut clinic. RGCCs technique for DC production is partially different than that ofdr. Nesselhut, i.e. RGCC may produce DCs by priming them with the circulating tumor cells (CTC) in the blood. This is relatively special technique that can not be done by many to my knowledge and RGCC is probably the best in this since they are very experienced at capturing the CTC (typically used for the chemo sensitivity tests). While I think RGCC can use tumor samples too for priming the DCs, with this technique there is no need for a tumor sample but only some blood sample.
Ref for fig. above http://www.dendriticcellresearch.com/denvax
Once we decided to go for DC treatments, here are a few additional supplements and drugs that can be considered to be used as a supportive strategy for the DC therapy:
Addressing (inhibiting) Tregs
- Cimetidine 800mg/day (Ref)
- Metformin 1000mg/day – 2000mg/day
- Cyclophosphamide 50mg 3x/week (as used by Prof. dr. Dana Flavin)
Addressing tumor microenvironment – making tumor surrounding less acidic in order to support the T-cell function:
- Lanzoprazole or Omeprazole, e.g. 40-80mg/day
- Statins (MCT1 inhibition), e.g. Medastatin at 40mg/day
- Resveratrolat 500mg/day
- Other proton transport inhibitors such as Amiloride 15-30mg/day, Acetozolamide 200mg/day
- 2DG would also leadto reduced proton output (1-2g/day)
- DCA20mg/kg/day and Alpha Lipoic Acid600-900mg/day will lead to reduced acidity
- Thalidomide has a strong capacity to boost immune responses and is therefore referred to as immunomodulatory drug; indeed it has been demonstrated that thalidomide has immunomodulatory properties, resulting in T-cell costimulation (Ref) and natural killer (NK) cell and NK T-cell activation (Ref1, Ref2).
- A TLR4 agonist synergizes with dendritic cell-directed lentiviral vectors for inducing antigen-specific immune responses http://www.sciencedirect.com/science/article/pii/S0264410X12001120
Intratumoral TLR-4 Agonist Injection Is Critical for Modulation of Tumor Microenvironment and Tumor Rejection http://www.hindawi.com/journals/isrn/2012/926817/
Immunomax is TLR4 agonist
- Ultra Low Dose Taxol (see Taxol section) – 2.5mg/day
Paclitaxel in ultra-low concentrations was also able to support differentiation of MDSC into functionally active DC. http://omicsonline.org/open-access/lowdose-chemomodulation-and-cancer-vaccines-2157-7560.1000e126.pdf
- Probiotics (see Probiotics section)
- Melatonin – immune system supporting supplements, 20mg/day before sleep
- Curcumin– immune system supporting supplements, up to 8-9g/day is safe
- Diflunisal and Aspirin in high dose IV will create a pore structure in tumor cells membrane (see Diflunisal section)
- Local Hyperthermia, 60-90min before DC administration
- Low sugar diet
- To support various components of the immune system: Coriolus,Cordyceps, Reishi, (I buy them from here:http://www.hawlik-vitalpilze.de),Fucoidan, Agaricus.Anothersource that seem to be good ishttp://www.fungi.com/
- TLR7 agonists such as Imiquimod: The TLR7 agonists imiquimod and gardiquimod improve DC-based immunotherapy for melanoma in mice http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4002679/
Cancer immunotherapy via dendritic cells Cancer immunotherapy attempts to harness the power and specificity of the immune system to treat tumours. The molecular identification of human cancer-specific antigens has allowed the development of antigen-specific immunotherapy. In one approach, autologous antigen-specific T cells are expanded ex vivo and then re-infused into patients. Another approach is through vaccination; that is, the provision of an antigen together with an adjuvant to elicit therapeutic T cells in vivo. Owing to their properties, dendritic cells (DCs) are often called ‘nature’s adjuvants’ and thus have become the natural agents for antigen delivery. After four decades of research, it is now clear that DCs are at the centre of the immune system owing to their ability to control both immune tolerance and immunity. Thus, DCs are an essential target in efforts to generate therapeutic immunity against cancer.