We have recently reported the ability of a heat killed injectable mycobacterium product known as IMM 101 to induce clinical remissions in advanced melanoma and to enhance survival in a randomised study in advanced pancreatic cancer patients when added to Gemcitabine versus Gemcitabine alone. IMM 101 induces activation of the innate immune response especially NK and gdT cell activation. In addition it boosts TH-1 cell immunity responses and appears to enhance the response to other modalities including chemo and Radiotherapy and especially to Ipilimumab and Pembrolizumab. Unlike other combinations there is no added toxicity.
Other Immune-modulators include the IMiDs such as Lenalidomide which greatly enhances cell mediated and antibody responses to vaccines in both murine models and humans, and in addition it enhances ADCC and responses to antibodies such as Rituximab. The favourable effect of immune modulation would appear to involve the ability to inhibit T reg and Myeloid derived suppressor cells. Lenalidomide is very effective at inhibiting T reg cells. However, a number of drugs such as cyclophosphamide can also enhance this effect as and are most effective at low and hence relatively non toxic doses.
Naltrexone which is an anti opiate receptor blocker also induces marked immune modulation only at low doses (LDN). In addition to its effect on opiate receptors we have recently reported that it is a strong antagonist of TLR 9 which could explain its marked anti inflammatory effects on Crohns disease. Its effect on immune-modulation may be explained by its differential effect on gene expression at low and high doses. At low doses LDN is non toxic and enhances other immunotherapy modalities.
CBD and THC are cannabinoids which have no cytotoxic activity yet we have reported that they enhance responses to radiotherapy in the mouse glioma model and that the effect is more marked when given metronomically in a number of cell line assays. We will report on combinations of these agents as well as new clinical studies.
In addition it will be stressed that IMM 101, the IMiDs and LDN all require high vitamin D3 ( A hormone!) levels to be effective.