The fact that effective defense resources are present at a higher level does not mean that they inevitably will act at a lower level.

This view of the abnormal immunological processes in cancer has pointed the way for some new therapeutic approaches. From the therapeutic point of view, the problem becomes one of how to induce the body to regain, at the necessary level, the lost immunological capacity, and through a specific allergic defense, to combat the cancerous entities. Furthermore, since this specific allergic defense capacity is lost independently by the various levels of organization, the immediate problem would be how it could be recovered for the particular level where the loss occurs. The existence of adequate defense capacity at a higher level, such as the systemic, does not provide a solution for cancer present at lower levels such as the tissular, because of the independence which exists between levels. Only the manufacture of coagulant or immune antibodies against cancer at the proper level would put the individual in a sufficiently active defense phase to enable him to resolve the condition at that level.

The problem of immunity at the proper level thus appears to be critical for any immunological attack against cancer. It is evident in other conditions as well and has inspired the use of local vaccination in localized infectious conditions. (307, 308)

The study of immunity against viruses has permitted us to recognize the importance of immunity at different levels. Virus infection is a typical cellular condition, the virus multiplying only within a cell. Theoretically, an immunity at all levels can be induced for viruses. According to the view discussed above, however, a systemic immunity with circulating antibodies will not insure a cellular defense. It would intervene only when the virus is passing through the systemic level and its activity would last only during the time when circulating antibodies are present. During this time, the virus will be prevented from reaching the cells. Once the circulating antibodies are no longer present, the cells cease to be protected. For an efficient defense against viruses an immunity within the cell appears thus to be indispensable. The use of dead virus vaccine will induce only systemic immunity, which can be recognized through the circulating antibodies. It is unlikely that the killed virus enters the cells. It does not affect them, and consequently does not induce cellular immunity. Even a mild cellular infection with living virus will give the necessary long lasting cellular immunity. This would explain the need for living and not killed vaccines for viral infections, as first postulated by Pasteur.

A similar level immunity can explain the differences seen between the immunity resulting from the use of microbial vaccines and that produced by natural disease. Typhoid infection gives lifelong immunity; the vaccination, only relative and temporary immunity. An explanation can be found in the fact that, in the disease, along with the septicemia, manifest changes occur in organs and tissues. Spleen and lymphatic tissues are highly affected in typhoid and it is possible that the development of the defense at their level would explain the lifelong immunity that follows the natural infection.

In cancer, the problem would be to induce not a systemic defense, which is still present for invasive cancer, but an effective tissue or even cellular defense. Immunological treatment of cancer would have to make tissular and possibly cellular levels regain their capacity to defend themselves through efficient allergic responses. The immunological prevention of cancer would lie not in the creation of this defense or in increasing it quantitatively but enhancing it qualitatively. A successful allergic defense at this level apparently would have a preventive and even curative effect. The use of lipids in the induction of the defense mechanism against tissues has an interesting application in cancer. A systemic treatment with lipids or lipoids can change the defense response so that it can be effective at a specific level where it is otherwise inadequate. For invasive cancer, the lipid activity must be induced at the cell level. The active lipoids for this purpose are those with a high affinity for the cancerous cell.

As abnormal cells in general show similar capacity to bind the lipoids administered, this general affinity becomes a handicap if abnormal entities other than cancerous cells are present. These considerations have led us to attempt to use methods which will insure the activity of lipids at the cell level.

In one of these methods, the chosen lipoids are brought directly into contact with cancerous cells through local injections into the tumors. Single injections produce only limited changes in tumors. Local injections repeated so as to insure the presence of the lipoids once, and then again 15 days later, are required to induce an effective response. The lipoids or lipids are so chosen that, when bound to body constituents they will induce allergic or immune defense responses. The acid lipids of tubercle bacilli, bixine or guinea pigs are especially prone to induce allergic reactions, while the lipids of microbes—such as coli, typhoid or diphtheria —produce immune responses.

In another method, lipids chosen were bound to cancerous entities in vitro. Cancerous cells were obtained and treated in vitro with lipids under whose influence the body is able to manufacture allergic or immune antibodies. Colloidal suspensions of the lipids or lipoids were prepared as mentioned above, mixed with suspensions of cancerous cells, kept at 37°C for a few hours, then separated from the non fixed lipids and injected into patients. In order to obtain good results it was necessary to inject this material at least twice, at an interval longer than two weeks, in order to insure an allergic reaction against the cell lipid preparation. While a single injection produced good results only in a very small number of cases, repeated injections were manifestly more effective. When cancerous tumor cells could be obtained through biopsy from the patient, we used them for the in vitro treatment with lipoacids. When biopsy material was not available, we used cancerous cells of similar origin as the tumor of the subject, preferably pooled.

The condition for success of these methods has appeared to be the presence of the cell lipid complex at the moment of appearance of antibodies. This is assured only by the repetition of the injection. Another interesting aspect of the immunological problem in cancer, related to loss of the natural defense mechanism, is the loss by cancer entities of their capacity to utilize certain elements known to intervene in the defense mechanism. The role of magnesium in the properdin system, copper in cytochrome oxidase, of calcium in general defense, suggests a correlation between their deficient utilization in cancer and the loss of the defense. We will discuss this problem below, after reviewing the pharmacological aspect of these elements.