CANCER IMMUNOLOGY

Coordinators:

Dr. William D. Terry Dr. Yuichi Yamamura

The joint seminar entitled “Immunotherapy of Cancer and Its Fundamental Bases” was held in Hawaii March 1975, to discuss the fundamental aspects of cancer immunotherapy and its possible clinical application. The subjects covered during the discussions included immunotherapy with BCG and related materials, immunopotentiators other than BCG, immunotherapy with transfer factors or cells, immune evaluation and other types of immunotherapy.
The highlights of the seminar included the induction of tumor immunity, protection of regional lympnode metastasis, and the rejection of rechallenged tumor, by injection with living BCG cell wall fractions. Some of the important factors for successful adjuvant therapy raised by the U.S. side: 1) immune-responsiveness of the hosts, 2) tumor size and 3) doses of BCG. The other aspect raised in this seminar was the failure of inducing systemic tumor immunity by BCG application to an experimental model using MC-induced, murine autochthonous tumor lines in early transplant generations.
Overall the application of BCG and BCG fractions to immunotherapy of human cancer has been confirmed as one of the most important subareas in cancer immunotherapy as revealed in the “Compendium of tumor immunotherapy protocol No.2” published by the Office of International Registry of Tumor Immunotherapy, NIH. Recent results of BCG immunotherapy on human cancer patients were summarized. Positive skin reaction to dinitrochlorobenzene (DNCB) was also discussed as a differential marker in the application of BCG immunotherapy. Application of cell wall fraction of BCG can avoid several side effects of living BCG. Combination therapy of BCG and chemotherapy was also discussed.
The principal chemical structure of the purified cell wall was shown as the polymer of “mycolic acid-arabino-galactan mucopetides.” This polymer has been proved to be a potent adjuvant to induce circulating autibody and cell-mediated immunity.
Immunopotentiators other than BCG, such as the cells of Corynebacterium pavum, Serratia Marcescens, Streptococcus pyogenus, and Streptococcus hemolyticus were also discussed. Although these bacterial cells were treated with phenol, formalin or penicillin, they still showed serious toxicity in the patients. Other types of immunopotentiators such as levamisole, lysolecithine and its analogues and secalonic acid D were discussed. Toxicity of secalonic acid D was reported to be reduced to one tenth by tetrahydropyramylation, without the loss of adjuvant activity. Clinical evaluation of the agents awaits future investigation.
The third aspect of the joint seminar was immunotherapy on such immunodeficient disease as cancer with transfer factor or modified tumor cells. Modification of immunogenicity by virus infection or neuraminidase-treatment was reported. Immunological responsiveness of tumor-bearing hosts were also discussed: T-cell activity was markedly depressed, but B-cell activity retained at the normal level. The suppression of T-cell activity was reported to return to normal by administration of lentinan or BCG cell wall skeleton. Impairment of cell mediated immunity of most cancer patients was detected by depressed in vitro responsiveness of lymphocytes to the mitogens, and was closely correlated to the clinical stages and the prognosis.
There were lively discussions on each of the main and individual topics presented by the participants, providing for interchange of information and ideas. In addition, there was great interest expressed in clinical immunotherapy by both sides, resulting in an agreement to hold the second seminar on cancer immunology, focusing on the problems and current research in clinical cancer immunotherapy. The meeting is planned for March 1 976 in California, U.S.A.
As for the exchange of personnel, five Japanese scientists were sent to the U.S. for collaborative studies on cancer immunotherapy by modified cancer cell inoculation and immunological parameters in cancer patients before and after the surgery. This experience has been quite beneficial to the Japanese scientists. It is felt that more efforts should be made in sending additional American scientists to Japan.