22. Why is an immune reaction, not taking place at the time when a cancer is formed in the body, established when the cancer tissue is returned to the body as a vaccine?
- The key points are injection with adjuvant so that fragments of autologous cancer tissue are directly incorporated into dendritic cells in the body. This high uptake capacity of immature dendritic cells in the body is taken advantage of. Upon ingestion, it transfers to the regional lymph node, where it matures, stimulates helper T lymphocytes, and further activates killer T lymphocytes (especially CTL) through it. When it moves in the body with blood flow, when it comes into contact with cancer cells, it further activates and kills cancer cells while proliferating. If cancer cells are killed, it can be interpreted that cellular immunity has been established. In the state of nature cancer cells are energetic so fragments do not arise from cancer tissues and rarely are taken directly into dendritic cells in the body.
- In order to establish cell-mediated immunity, it is necessary for the cancer cell side to contain cancer antigen, at least to some extent. Although this amount is small, it is completely unknown how much it is necessary in practice. In the case of postoperative liver cancer, autologous liver cancer vaccine clearly has the effect of suppressing the recurrence of liver cancer if it is from 1 gram or more of formalin-fixed cancer tissue (Peng BG, et al. , Jpn JCancer Res 93: 363-8, 2002). Based on our experience, other types of cancer patients saw some margins 1. More than 5 grams are needed. However, this may differs greatly depending on the type of cancer and the individual situation.
- Another important thing is that if MHC-class I molecule is expressed on the surface of cancer cells remaining in the body and no cancer antigen peptide is presented on it, CTL cannot be recognized as abnormal cells That is the point. Expression of MHC-class I is usually said to be infrequent, and one way to stimulate this is IFN-? administration. Some researchers have produced IFN – ? in the body using bacterial components such as BCG – CWS instead of IFN – ? administration. Depending on the type of cancer cell, IFN-? administration may cause MHC-class I expression to be elevated (not necessarily in all cases) and is likely to be killed by CTL.
23. Do you use other people’s materials such as plasma and serum?
We do not use plasma or serum as it is. However, a small amount of human serum albumin is contained in autologous cancer vaccine as a kind of stabilizer. This human serum albumin is a medical drug that is heat-treated so that possibly latent viruses are eliminated without risk.
24. For example, if you have metastasis at two 2 locations with gastric cancer, do you need to make a vaccine from a mixture of cancer tissue. Do you need 1.5 grams or more of each of the two cancer tissues?
No, if the cancer is originally the same, if both the cancer body itself is 1.5 grams or more, you can make a vaccine.
25. Histologically, various organs are made up of a wide variety of cells. In such a structure, it seems that cancer antigens are diverse, and is it impossible to obtain a wide variety of cancer antigens sufficiently quantitatively from 1.5 grams of one cancer tissue?
Yes, that possibility cannot be ruled out. However, the amount of cancer antigen protein in cancer cells is very small. It is too small to measure. Since almost all malignant cancer cells are composed of the same protein as normal cells, only a very small amount of cancer antigen peptides is present the cell surface. Nevertheless, if properly activated immune mechanism, you can discriminate a very small amount of cancer antigen peptides presented on cancer cell surface. So, even if normal tissues are mixed, this does not become a big problem. You only have the minimum amount of cancer antigen that can stimulate the immune system. However, as it is assumed that this minimum amount varies widely among individuals, it is currently the case that efficacy can only be determined by clinical results after autologous cancer vaccine administration.
26. Do you think that all tumor cells are always expressing cancer antigens? If cancer of a type not expressing a cancer antigen exists, it seems impossible to have autologous cancer vaccine therapy?
There are cancer types that do not express cancer antigens. A method of examining whether or not a cancer cell in a patient’s body is expressing a cancer antigen (although it may be possible if there a cancer antigen has already been identified), in the case of targeting against antigens, has not yet been developed.
Nevertheless our autologous cancer vaccine is characterized by its ability to activate immune cells with an unspecified number of unidentified cancer antigens as clues. The choice as to which cancer antigen to use is left to the immune mechanism in the body. As this happens within the body of the same individual, even a very small difference between normal cells and cancer cells can be distinguished. Like a synthetic vaccine, it is not a method of artificially adding antigens from outside the body (the result although desirable may be disappointing).
For that reason, the drug is customized to the individual patient and cannot be used by others.
27. Many anticancer agents cause immunosuppression. Is it possible to combine anticancer drug therapy with autologous cancer vaccine therapy?
In principle, it is possible to use it in combination as long as it is an anticancer drug that does not intensively inhibit lymphocyte proliferation. Also, there is a possibility that self cancer vaccine therapy is administered during the drug withdrawal period of anticancer drug administration or low dosage of anticancer drug is administered. If possible, wait for 4 weeks from entering the drug-free holiday until the effect of anticancer drug disappears, confirm that the number of lymphocytes in the blood is on the way to recovery, and there is still 6 weeks left for autologous cancer vaccine administration. Following this schedule is desirable. If a patient has had a lymphocyte deficiency even once, it must be confirmed that there is a definite recovery. For an example of a case where recovery took a long time, see this paper (? S u YB, et al., JC lin Oncol 22: 610-6, 2004).
However, even in the case where an anticancer drug of relatively weak myelosuppressive effect is administered in a smaller amount than usual, even in the course of administration of FOLFOX or FOLFIRI, the number of blood lymphocytes can be maintained at a constant number or more. When this is the case, simultaneous use is possible. In addition, what has recently appeared and is referred to as molecular targeted drugs or antibody drugs, can be used in combination if it does not inhibit T cell proliferation. As this field is steadily progressing, the conventional thinking about combination use is changing drastically.
28. Are there any worries about immune tolerance and conversely about autoimmune diseases?
I have not seen any of this in the over 1800 cases so far administered. However, because the cancer antigen is unidentified, it is not a strict investigation, and there is no clinical problem which is thought to be due to immune tolerance. On the contrary, it does not cause symptoms similar to autoimmune diseases. The immune system in the body seems to exert extremely severe discriminatory power.
29. I heard that “cancer” is different in nature depending on where it originally occurred. In my case, “cancer” originally occurred in the adrenal gland and spread to the lungs. Is there any effect in such cases?
Autologous cancer vaccine is a Phase I / Phase II early clinical trial demonstrating the effect of suppressing recurrence of liver cancer · prolongation of overall survival time (Clinical Cancer Research, 10: 1574-1579, 2004). Even in cancer other than liver cancer, the way of making the vaccine is the same and uses the patient’s own cancer tissue as raw material, so it can recognize the abnormal marker (TAA, cancer antigen) lurking in it If the vaccine succeeds in activating killer lymphocytes in the body, it will probably be equally effective no matter to where the cancer subsequently spread.