SUMMARY REPORTS OF EXCHANGE SCIENTISTS

(1) Moriwaki, Kazuo
National Institute of Genetics, Department of Cytogenetics
Yata-1111, Mishima, Shizuoka-ken, Japan

Sponsor and Host Institution:
Dr. Igor B. Dawid, Laboratory Chief, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, NIH, Bethesda, MD.
Dates of Visit:
Sept. 8: City of Hope Research Institute, Durate, California
Sept. 9: California Institute of Technology, Pasadena, California
Sept. 12: Memorial Sloan Kettering Cancer Center, New York
Sept. 13: Rockefeller University, New York
Sept. 14: Harvard University Medical School, Department of Genetics, Boston
Sept. 15: Harvard University Children’s Hospital Medical Center, Boston
Sept. 17: Smithonian Institute, Washington, D.C.
Sept. 19: National Institute of Child Health and Human Development, NIH, Bethesda
Sept. 20: Monell Chemical Senses Center, Philadelphia

Summary of Activities:
1) City of Hope Research Institute, Division of Biology, Molecular Genetics Section.
Items discussed with Drs. K. Itakura, K. Yokoyama and B. Wallace are as follows: Technical problems in the chemical synthesis of MHC DNA. Molecular mechanism emerging extraordinarily large genetic polymorphism in mouse H-2 complex. Development of H-2 DNA probe specific to the K region sequence. Nucleotide sequence in Qa-Tla regions. Evolutionarily conservative nucleotide sequences on H-2 DNA. A seminar was given in this section entitled “Genetic status of Japanese wild mice and its implication to the origin of laboratory mice”.
2) California Institute of Technology, Molecular Biology Department.
Dr. L. Hood’s laboratory was the major purpose of this visit. Their laboratory facilities for sequencing DNA and amino acids were amazing. Detailed discussion was achieved with many scientists in this laboratory such as Drs. A. Roach, M. C. Zuniga, M. Malissen, E. Rothenberg, on H-2 and IA/IE molecular structure especially those of the mutant DNAs. Biological significance of NO.15 chromosome in mice was also one of the topics.
3) Sloan Kettering Memorial Institute
First visit was Dr. E. A. Boyse’laboratory. His congenic mouse strains as to Tla region were major aim. Important knowledges on these mice were obtained. Detailed explanation on the mouse monoclona antibodies against Lytantigens was given by Dr. N. Tada. In Dr. L.J.Old’s laboratory, many culture lines of human cancer were demonstrated. Cytogenetical detection of oncogene unique sequence was shown in Dr. W. S. Hayward’s laboratory, actually by Dr. R. S. K. Chaganti and Dr. S. C. Jhanwar. Advantage of the use of testicular cells for the high resolution banding was shown. Dr. K. Artzt had focused her genetical study on the chromosomal arrangement of H-2 complex in t mutant mice.
4) Rockefeller University
Dr. Stark in the Laboratory Animal Department gave us Claude mouse strain which was developed by Dr. E. Reich as a highly susceptible line for the kidney tumor.
5) National Institute of Child Health and Human Development, NIH
Dr. I Dawid told the basic idea on the molecualr genetic study of transposable genetic element from view point of evolution. Dr. H. Okayama demonstrated precisely the experimental procedures for the preparation of a larger size cDNA probe carrying SV-40 derived promotor sequence. In Dr. K. Ozato’s laboratory, DNA transfection experiment with the synthesized mutated H-2 DNA was being achieved.
6) Harvard Medical School, Department of Genetics
Discussion with Dr. Seidman was made on DNA cloning of H-2 S region gene. Dr. C. Morton demonstrated detailed procedure for in situ hybridization technique to detect oncogene sequence. Importance of the use of DNA probe which does not contain Alu family was stressed.
7) Children’s Hospital Medical Center in Harvard Medical School
Dr. Latt showed the isolation of metaphase chormosomes by Cell Sorter and purification of the specific DNA from the isolated chromosomes. In situ hybridization technique was also demonstrated in this laboratory.



(2) Kokichi Kikuchi
Department of Pathology, Sapporo Medical College

Sponsor and Host Institution:
Dr. Lloyd J. Old Head, Division of Immunology, Memorial Sloan-Kettering Cancer Center Dr. Ronald Levy Associate Professor, Division of Oncology, Stanford University School of Medicine Dr. Paul Terasaki Professor, Department of Surgery, UCLA School of Medicine
Dates of Visit: from Sept. 28, 1983 to Oct. 17, 1983

Summary of Activities:
[Objectives] To discuss (A) the clinical approach to immunotherapy of cancer with anti-cancer cell monoclonal antibodies (MoAb) and (B) present status of detection of tumor specific antigens
[Achievements]
(A) Current status of immunotherapy of leukemia and malignant lymphomas with MoAb was discussed. In Stanford University Medical Center, T cell leukemia/lymphoma was treated with MoAb-Leu-1 and other anti-pan-T MoAbs. They obtained some effectiveness in some patients, although it was not remarkable. I suggested to use MoAbs, which are not reactive to broad spectrum of T cell lineage, but are directed to a limitted subpopulation of normal T cells and possibly reactive to tumor cells. We have developed many MoAbs of this kind. Treatrnent of B cell leukemia/lymphoma with anti-idiotype MoAb seems ideal since it is confined to the B cell tumor. This therapy was effective, especially in the first case. We discussed the importance to examine the local resposiveness of hosts in tumor tissues with immunohistological methods which we could contribute by supplying MoAbs to lymphocyte subsets and technical aids. Dr. Kon, one of my colleagues will join the research team.
(B) Production of anti-cancer cell MoAbs and their application for cance immunotherapy were tried in UCLA. The industry of MoAb production in Dr. Terasaki’s laboratory was very impressive. It was computerized in every point and automated as possible as one could. We have developed MoAbs to malignant melanoma and pancreatic carcinoma, however, their tumor-specificity has not been established. Many of their MoAbs had proved to be directed to blood group related antigens after more advanced investigations. We agreed in the significance of immunohistological examination to determine the specificity of MoAbs. We are cooperating by sending one of my colleagues, Dr. Kasai, who is engaged in the screening with immunoperoxidase method. Immunotherapy of solid cancer with MoAbs was told to be not effective at the time I visited.
(C) Development of human-human hybridomas secreting MoAbs to human cancer is essential for immunological treatment of cancer with MoAb. Dr. Old’s laboratory were producing many MoAbs to human melanoma, breast cancer and leukemia cells. Information about the detailed technique and human HAT-sensitive myeloma cell lines was provided. (D) Present status of detection of tumor-specific antigens was discussed. In Dr. Old’s laboratory, MoAbs to cancer cells were used for identifying tumorspecific antigens in molecular level, however, it seemed unsuccessful so far. On the other hand, individually specific antigen is identified serologically by patient’s sera, although the successful cases are not many. In our hands cell-mediated immunity to autochthonous tumors of the rat has been demonstrated by identifying immunocyte subsets with MoAbs to rat lymphoid cells which have been developed in our laboratory. We discussed on the existence of tumor-specific antigens and exchanged the informations.
List of Publications Resulting from This Study:
(A) Kikuchi, K., et al.: Significance of local T cell response to human cancer. In; Toris, M. ed., Basic Mechanisms and Clinical Treatment of Tumor Metastasis. Acad. Press, New York, in press
(B) Kikuchi, K., et al: Immunopathological studies on B cell malignancy utilizing newly-developed monoclonal antibodies. Jpn. J. Cin. Oncol. 13: 517-532, 1983
(C) Ishii, Y., Kikuchi, K., et al: Lymphocyte subsets within the autochthonous rat tumors undergoing rejection as defined by monoclonal antibodies. Cancer Res., submitted
(D) Matsuura, A., Kikuchi, K., et al: Rat T Iymphocyte antigen homologous to mouse Lyt-1 and Lyt-2,3 antigen system. J. Immunol., in press


(3) Fujiwara Hiromi
Institute for Cancer Research, Osaka University Medical School. Associate Professor, MD and PhD

Sponsor and Host Institution:
Drs. Richard Hodes & Keiko Ozato, National Institutes of Health
Dates of Visit: Oct. 30, 1983 - Nov. 21, 1983

Summary of Activities:
l) With Dr. Ozato in NIH.
The purpose of my stay in NIH is a) to learn techniques in the field of molecular biology, b) to obtain new informations and c) to discuss our collaborative studies. I discussed with several investigators of Dr. Ozato’s laboratory on a) genetic control of hapten-CTL responses and gene cloning of H-2 gens, b) exon shuffling of H-2 gene and c) in vitro mutagenesis of H-2 genes. I have also acquired techniques for the gene cloning, DNA-sequancing, DNA-transfection and purification of mRNA. We discussed about our future collaborations on functional and molecular characterizations and gene cloning of H-2 gene.
2) Seminar entitled “Augmented induction of tumor-specific immunity by helper T cells and its application of immunotherapy model”.
I made a seminar entitled above in NIH. After the seminar, I discussed about “Establishment of tumor-specific immunotherapy model” with Drs. R. Hodes, K. Ozato, G. M. Shearer and their fellows.
3) With Dr. S. I. Katz in NIH
I discussed with Dr. Katz concerning the role of Langerhans cell in the induction and implementation of skin-immunology such as contact sensitivity. Since we have had collaborative experiments, we exchanged new informations and designed further collaborative experiments.
4) With Drs. M. I. Greene, S. Burakoff and A. Maxam, in Boston area.
The purpose of my visit to Boston is to obtain new informations on DNA transfection. I have learned techniques for DNA transfection utilizing newly established fibroblast cell line in Dr. Greene’s laboratory, and new methods for exon shuffling of H-2gene in Drs. S. Burakofrs laboratory.
We have also discussed on the future perspective of tumor immunology including the establishment of tumor-specific immunotherapy and molecular biological analysis of TATA. I discussed with Dr. A. Maxam mainly on the diversity of TATA and the mechanism of generation of such diversity. Through 3 weeks’ stay in U.S.A., I have obtained many new informations on a) tumor immunology and b) molecular biological approaches for gene analysis of cell surface antigens. I have also acquired several techniques in the field of molecular biology.


(4) Noboru Kuzumaki, M.D., D. Sc.
Cancer Institute, Hokkaido University School of Medicine, Sapporo, JAPAN

Sponsor and Host Institution:
Dr. Stephen J. O’Brien, Chief, Section of Genetics, Laboratory of Viral Carcinogenesis, Frederick Cancer Research Facilitles, National Cancer Institute, Frederick.
Dates of Visit: From March 25. 1984 to April 21, 1984

Summary of Activities:
1) I learned various fundamental techniques for moleculor biology dealing with oncogenes and their products. They include propagation of bacterial strains, isolation of plasmid DNA. digesting DNA with restriction enzymes, agarose gel electrophoresis, hybridization of Southern filters, in situ hybridization, extraction, purification, and analysis of mRNA from eukaryotic cells, and chromosome and isozyme analysis for somatic hybrid cells.
2) I had seminar concerning our research (Title: Correlation between an oncogene and tumor-specific cell surface antigens) at Dr. O’Brien’s laboratory and Dr. Law’s laboratory. I could get valuable comments from them.
3) I met quite a few people studying oncogenes in Frederick and Bethesda, and got very valuable new information about oncogenes and their products. I am sure that this is extremely useful for our ongoing projects.
From above results, I can say the Program assisted me very much in proceeding our research projects, and progress in our research was enhanced through this Program. I am planning to let a young scientist in my institute study at Dr. O’Brien’s laboratory in the near future. I would like to make the best use of the results, and contribute to research for Correlation between oncogenes and tumor antigens.



(5) Steven J.Burakoff, M.D.
Professor of Pediatrics, Harvard Medical School Boston, Massachusetts

Sponsor and Host Institution:
Toshiyuki Hamaoka, M.D. Professor, Department of Oncogenesis Director, Institute for Cancer Research Osaka University, Osaka, Japan
Dates of Visit: August 20 to September 3, 1983

Summary of Activities:
Fortuitously this trip coincided with the Fifth International Congress of Immunology which was held in Kyoto, Japan from August 21st to August 27. While at the Congress I had the opportunity to chair a workshop #220 entitled, “T-T cell Interaction During the Induction of Cytotoxic T Cell Response and Long Trem Culture of the T Killer Cells”. This workshop was shared in collaboration with Professor K. Saito. This was an extremely informative workshop in which there were presentations by speakers from many countries, including the United States and Japan. Work was presented by Dr. Hamaoka’s group from Osaka University, by Dr. Fujimoto’s group from Kochi Medical School, and by Dr. Hinuma from the Institute for Virus Research at Kyoto University. During the Congress on August 24th, Dr. Hamaoka and the Osaka University held an informal discussion group in which the future prospectives of immunology were discussed.
I then had an opportunity to participate in the U.S. Japan Immunology course organized by Drs. William Paul and Dr. Takamitsu Kishimoto which was held at the Fuji Seminar House from August 28-3lst. During this time I had the opportunity to present some of the work from my laboratory and I also had an opportunity to interact with a number of Japanese participants. Besides Drs. Kishimoto and Hamaoka this included, Dr. Masaru Taniguchi from Chiba University, Dr. T. Sasazuki from Tokyo University. I had a chance to talk with many of the best postdoctoral and predoctoral fellow in Japan that have been especially selected to attend this course.
From September 1-3rd I was the guest of Dr. Hamaoka at Osaka University. I gave a formal lecture on September 1st to the immunologists at Osaka University and on September 2nd met with members of Dr. Hamaoka’s group to discuss their research.
As a result of this visit a member of Dr. Hamaoka’s research group Dr. Yasuyuki Takai will be joinig my laboratory for several years in September, 1984 as a postdoctral fellow. I may also accept as a fellow Dr. Y. Nishimura from the laboratory of Dr. T. Sasazuki of the University of Tokyo. This opportunity to visit Japan was extremely fruitful for me, not only did I have the opportunity to meet with many of my Japanese colleagues, but through the tenure of several of their fellows in my laboratory a number of , collaborative research efforts have been initiated.