In medical literature there are cases of histologically proven malignant tumors that spontaneously disappeared. At the time the cause was quite unknown.
In the early 1960’s a possible explanation for these apparently miraculous regressions was postulated. At this time it became evident that some malignant tumors were recognized by the host as being foreign; the host produced general and perhaps specific immune activity. This new concept is under intense scrutiny, the aim being to identify specific tumor substances which are capable of producing specific reactions advantageous to the host.
As might be expected, patients with deficient immune systems – whether it be secondary to congenital anomalies, or an aging process, or immunosuppressed from drugs or irradiation – are more apt to develop malignant tumors than the normal population. A classical example of this is shown in patients who, having undergone renal transplantation requiring immunosuppressive therapy to prevent rejection of the transplanted organ, are at a significantly higher risk of developing cancer than a normal group of people.
Furthermore, patients in a poor nutritional state with a large tumor load respond poorly when challenged by a specific antigen.
It has become apparent that the body’s immune surveillance system is an extremely complicated process, involving formed elements; that is, numerous wandering cells – fixed as well as highly mobile – antibodies, and protein. Once the surveillance system has been challenged or activated, both general and specific responses occur, which, in summation, are advantageous to the host.
As might be expected, the immune system is widespread throughout the body, and although an initiating response may occur locally (such as in the skin), the response is not limited to that organ, but can become quite generalized. For example, a delayed hypersensitivity reaction of the skin can be accompanied by elevation in white cells, T and B lymphocytes, fever, and changes in protein metabolism.
Over the last twenty years or so I have noticed that patients with large tumor loads remaining after the removal of the primary tumor and who developed generalized allergic skin reactions have lived longer than I expected. In brief, where there was skin rash, the patient lived longer.
It seemed not unreasonable to suppose that one could, in experimental animals, modify the behavior of transplanted malignant tumors by producing allergic dermatitis. Furthermore, it seemed reasonable to use what might be described as a naturally occurring triggering substance.
Poison ivy is a well-known plant capable of producing a delayed hypersensitivity reaction in 60-80% of people exposed to it. The tar-like oil, urushiol, of poison ivy is the triggering substance. Chemically, this is a naturally occurring benzene derivative, 0-di-hydroxybenzene, with a fifteen carbon side chain the benzene moiety, a naturally occurring catechol.
Let us briefly compare the compound di-nitrochloro-benzene, a drug currently being used in immunotherapy. This chemical is now being used in the management of certain malignant skin lesions as a triggering substance to cause delayed hypersensitivity reaction as manifested by a skin reaction. Di-nitro-chloro-benzene also contains a benzene ring without a complex carbon chain, nor does it include the catechol component. Nevertheless it is useful in controlling malignant and pre-malignant skin lesions.
The following laboratory experiment was arranged. In this endeavor I had the good fortune to have the aid of two well-trained laboratory technicians, Beverly Densmore and Sue Slepak.
Twenty-nine Balb-C mice (inbred strain) were divided into two groups, 19 treated and 10 control. The mice in each group were 61 days old at the commencement of the experiment. Those in the treated group were sensitized by applying crude extract of poison ivy (400 mg/ml) to the ear skin of the mice in this group. Six days later a challenge dose was applied to these mice in the same manner. One day later pleomorphic cell sarcoma (cell number significantly greater than 102) was transplanted into the soft tissue of the loin of both the treated and control group.
The controls and treated mice were then separated to prevent inadvertent contamination of the control group with poison ivy. The treated and control groups were managed identically except that those in the treated group were exposed to a daily challenge with the extract to maintain active allergic dermatitis.
One week after transplanting, the tumors in the control group were significantly larger than those in the treated animals. The growth of tumor in the control group advanced as expected with 100% mortality at 39 days after transplant, the mean survival time being 33.7 days. The expected survival time for this tumor as documented at Jackson Laboratories, Bar Harbor, Maine, is from 28 to 35 days. The survival time in our control animals did not significantly deviate from this expected survival time.
These pictures show the results in the controls and treated mice.
Ninety percent of the control animals had tumors of a large size–one or 10% had a slightly smaller tumor. Forty-five percent of the treated animals had tumors of a small size. No treated mice had tumors as large as in the controls, as evident in the pictures.
Initially, baseline white cell counts were done on the animals in each group. Throughout the experiment, the white cell counts in the control group remained at about the initial level. In the treated group, however, the initial dose of poison ivy produced a 200% increase in the total number of white cells; the lymphocyte series in the treated animals that developed skin rash reactions maintained extremely high levels.
In the control animals there was 100% mortality at 39 days, the mean survival being 33.7 days. In the treated group, fourteen died, the last death occurring at 45 days, with a mean survival of 37 days.* The remaining five of the treated animals were alive at 60 days with no clinical evidence of tumor – healthy, active, with fine coats of fur. Although this experiment is in some respects limited, it seems that the treatment significantly modified tumor growth.
At present, at Oakland University in Rochester, Michigan, techniques are being established to compile immunological profiles on healthy human volunteers. Baseline readings will be obtained. Subsequently, the volunteers will be challenged with poison ivy. It is anticipated that 60-80% will show delayed hypersensitivity reactions, as manifest by vesicular skin rash. As evaluated on skin reaction, 20-40% will act as a control group. It is anticipated that the majority will demonstrate changes in their immune profile; if these changes can be interpreted as being potentially helpful, it would not be unreasonable to apply this method of treatment to patients with proven malignant tumor.
Stage I carcinoma of the breast is described as a carcinoma which, when assessed by the present available methods, is limited to the breast, with no evidence of metastasis to regional lymph nodes, nor any evidence of hematogenous spread. Though the breast may be removed, five years later and with no other management, 20% show evidence of metastases. It is conceivable that subjecting patients with this stage of tumor to poison ivy might significantly reduce this 20% metastatic rate at five years. To the best of my knowledge no such study has ever been undertaken. If the volunteer study provides the anticipated hard data, I shall undertake such a study on human malignancy.
*(Ed. note:) It should be kept in mind that these mice are bred to accept a transplant, which is very different from the human system where a spontaneous breakdown in the immune system occurs. This breakdown is capable of repairing.