Although differences in metabolism from one species to another make it difficult to predict human efficacy from data in mice, this may not be applicable to therapies using the vitaletheine modulators. Unlike the metabolites of many directly cytotoxic drugs, the same probable progenitors and metabolites of vitaletheine are found in both rodents and humans. Similar responses from both murine and human immunocytes to ß-alethine and from murine and human red blood cell progenitors to vitalethine also predict similar efficacy against both murine and human cancers, assuming (of course) that the immune system is largely responsible for the therapeutic response as all of the data to date indicates.
This same assumption suggests limits to therapies with the vitaletheine modulators. Tumors growing at rates that kill before a secondary and even a primary humoral response can be mounted are not likely to be controlled by the vitaletheine modulators alone. These compounds would not be expected to work at all in models with tumors that outpace the humoral response or that grow in hosts that are immune-compromised by other lesions or factors. In other words, while athymic animals, nude rats or mice, s.c.i.d. mice, pathogen-free animals, animals on defined diets, humans on processed-food ("industrialized") diets, and especially germ-free animals may give appropriate responses to compounds directly toxic to tumor cells, a truly fair test of immune stimulants requires animals (or humans) that are otherwise immunocompetent and just lacking the stimulant or its nutritional precursor.
Large preexisting tumors might diminish the therapeutic capacity of the immune response by creating a phenomena known as tolerance, in which the tumor burden is so overwhelming that the host's immune system "decides" that destroying the large tumor mass may be more hazardous than trying to live with it. There are several possible explanations for tolerance and intractable tumor growth.
Regardless of the actual mechanism responsible for uncontrolled neoplasia, when the tumor is rapidly growing vitaletheine modulators should be most effective in combination with debulking ablative therapies. For example, even though recurrent melanoma in horses often does not respond conclusively to cryo-ablation alone, this technique does effectively diminish tumor burden and presents dead tumor cells to the immune system to act as on site vaccines against the tumor. At the same time cryo-ablation and breakdown of the tumor in poorly-sensitized horses might worsen the prognosis for the disease by loosing a few viable and metastatic tumor cells into the blood stream, which in turn can lodge in blood capillaries and spread the disease. Compounds stimulating the production of cytolytic antibodies such as the vitaletheine modulators, or even other less potent and more toxic immune adjuvants, theoretically sensitize immune responses toward released tumor cells, thereby helping to limit and control the growth of metastases. Note that the smaller cytolytic antibodies are simpler to mass produce than whole cells and should also diffuse more efficiently than immunocytes into interstitial spaces and occluded capillary beds to destroy tumor metastases.
In contrast to the irreparable harm to children when cancer is treated with conventional anti-neoplastic therapy (including mental retardation and other neurological and developmental problems), few obvious side reactions, if any, occur in weanling mice treated with the vitaletheine modulators. Normal development and life-spans appear to be possible with these new therapies. The similarities in the responses of mouse and human tissues to these compounds give reason to believe that little toxicity will be observed in comparable applications of the vitaletheine modulators in children with cancer.
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