REPORTS ON SEMINARS

(1) Seminar on “cell biology”

The 5th joint seminar in the Cellular and Molecular Biology Sub-area was held on the subject “Oncogene Products and Neoplastic Cell Growth”, at Gramercy Hotel, Washington, D. C. on October 17-19, 1983.
The meeting was convened by Dr. Benoit de Crombrugghe, NCI and Dr. Yoji Ikawa, Riken Institute, and had 4 sessions for understanding of the mechanism of cell transformation by cancer-related genes, “Generation of Viral and Cellular Oncogenes”, “Mechanisms of Oncogene Activation”, “Cellular Pathways for Transformation”, and “Grow Factors and Cell Surface Receptors; Potential Use for Drug Targetting.”
In the first session we discussed three examples of viral oncogenes, and their structural requirement for oncogenicity.
Dr. Hideo Iba discusses his work on the src gene in the laboratory of Dr. Hanafusa at the Rockefeller University. p60src has two major phosphorylation sites, one serine residue and one tyrosine residue. Each of these two residues was replaced by performing localized directed mutagenesis on a cloned RSV DNA. Substitution of one or the other residue does not modify the transforming activity of p60src and does not decrease its tyrosine kinase activity. In a second part of his talk, H. Iba compared the transforming activity of c-src and v-src. When v-src is entirely deleted and replaced by c-src the transforming activity of the resultant virus is much weaker. However, several hybrid RSV molecules containing portions of both v-src and c-src were as active as RSV containing v-src.
K. Toyoshima and T. Yamamoto first discussed the structural and functional similarities between the yes oncogene and the src oncogene as well as fps, fes and abl. All these oncogenes are distinctly related to each other and form a super src family. They all have a tyrosine kinase activity. They went on to discuss their analysis of a newly isolated avian crythroblastosis virus which contains only one oncogene the erbB oncogene. The structure of the protein was derived from the DNA sequence of the gene and a model was proposed depicting various functional domains in the protein.
Y. Ikawa, (Cancer Institute, Tokyo and Riken) discussed the structure of the leukemogenic glycoprotein (gp55) of Friend spleen focus-forming virus (SFFV). He presented evidence to show that the amino proximal 4/5ths of the protein of gp55 present a high degree of sequence homology with the gp70 env product of MuLV, whereas the following 66 amino acids are similar to p15 of Friend MuLV. The last 12 amino acids of gp55 are unique to gp55. The intriguing question is how a gene that is mostly derived from gp70 env and from DNA coding for p15 can become an oncogene?
A. Oliff (Rockefeller University) attempted to identify the leukemogenic sequences of Friend Leukemia virus (F-MuLV) and Mink cell focus forming (Fr-MCF) virus by constructing recombinants between these viruses and a non-pathogenic murine retroviruses. The recombinant viruses were assayed in vivo. He concluded that the envelope gene of Friend-MuLV plays a role in determining the induction of erythroleukemia.
During the second session two examples of how cellular oncogenes can be activated were discussed. S. Astrin (Institute for Cancer Research) examined the structure and expression of c-myc in a number of human hematopoietic malignancies. c-myc was found to be expressed at a high level in several leukemia and lymphoma patients. She found the c-myc gene to be rearranged in one African Burkitt’s lymphoma and in one non-Hodgkin’s lymphoma. S. Astrin proposed that in the other cases the increased c-myc gene expression I could be due to mutations in genes controlling the expression of c-myc and that elevated c-myc expression probably plays a role in hematopietic malignancies.
M. Shibuya (University of Tokyo) found c-myc gene amplification in two cases of gastric tumors but observed no amplification of ten other oncogenes. In particular c-mos, which is located on the same chromosome and in the vicinity of c-myc was not co-amplified with c-myc.
C. Croce (Wistar Institute) showed conclusive evidence that in some cases of Burkitt lymphomas there its a reciprocal chromosome exchange between the ends of chromosome 8 and the ends of chromosomes 14, 22 or 2. In each case the translocation results in bringing the myc locus near an immunoglobulin locus. This translocation causes the c-myc gene to be expressed at a higher level. Hybrids cells were produced between the lymphoma cells and mouse fibroblasts. In each the translocated myc gene maintains a high level of expression whereas in other hybrids between mouse cells and the HL60 cell lines, for example, the elevated c-myc gene expression characteristic of HL-60 cells, is shut off. The translocated c-myc gene and the normal c-nyc gene are, therefore, under different control mechanisms.
D. Lowy (NIH) compared the transforming activities in NIH-3T3 cells of the cellular and viral Ras genes. If the cellular Ras replaces the viral Ras in the full-length Harvey murine sarcoma virus, the resulting hybrid transforms NIH-3T3 cells very poorly. Three different mutant Ras genes which cause single amino acid changes in the cellular Ras gene give the Ras protein an increased transforming activity.
The third session examined possible cellular pathways for transformation and the role of polypeptides, like growth factors and the p53 protein, that are found in increased concentrations in transformed cells.
H. Mitsui (Niigata University) purified a novel transforming growth factor (TGF) from a rat cell line transformed by RSV. This polypeptide is acid-labile, in contrast to other TGF’s previously identified, and does not compete with Epidermal Growth Factor for binding to EGF receptors.
J. DeLarco (NIH) summarized studies on the isolation and properties of two other sarcoma growth factors produced in murine sarcoma transformed cells. The first competes for EGF binding and stimulates the growth of NIH-3T3 cells in soft agar, whereas the second factor has this same type of activity but only in the presence of EGF. It appears to modulate the growth stimulating properties of the first sarcoma growth factor.
A Hakura (Osaka University) has isolated and characterized cellular mutants that show a temperature sensitivity for transformation by Moloney Murine Sarcoma virus in a rat cell line transformed by this virus. These mutants are resistant to some but not all oncogenes.
M. Noda (Keio University, Tokyo) also isolated cellular mutants of Kirsten MSV transformed NIH-3T3 cells isolated as flat revertants. Enrichment for the mutants was achieved because the flat revertants exhibit a reduced sensitivity to ouabain. By cell hybrids studies M. Noda showed that the reversion phenotype is dominant over the transformed phenotype. The revertants are also resistant to retransformation by some oncogenes but sensitive to retransformation by other oncogenes.
A. Levine presented studies on the stabilization of the cellular p53 protein by the large T protein of SV40. P53 is a protein which appears to have a role in the regulation of the cell cycle. Its synthesis increases just before the increase in DNA synthesis begins in synchronized cell. The levels of p53 are also increased in embryonal carcinoma cells.
K. Segawa presented evidence that suggested that the middle T antigen has either an intrinsic or closely associated protein kinase activity. He also presented data that showed an effect of EGF on this protein kinase activity.
B. de Crombrugghe showed that the activity of the cloned!!!2(I) collagen promoter, after this promoter has been introduced in animal cells, is inhibited to the same extent as the endogenous a2(I) collagen promoter.
The last session focused on the structure of hormone receptors and their potential use in drug targeting.
M. Czech discussed the structure of the receptors for insulin and for insulin-like growth factors (IGF-I and II). He presented evidence showing a close structural and functional homology between the insulin receptor and the IGF-1 receptor.
I. Pastan discussed how hormones, viruses and other ligands enter cells by receptor-mediated endocytosis. The vesicles which are formed upon entry of the ligands into cells are called receptosomes. He showed that adenovirus has the ability to lyse receptosomes and empty its contents in the cytosol. Conjugates between a ligand (ex. an antibody to a specific receptor) and a toxin enter ceils through the same pathway. Addition of adenovirus increases the killing activity of the toxin conjugate, suggesting, therefore, a possible way to target toxins to cells carrying specific receptors in their membranes.

(2) Seminar on “Immunology”
The conference on “Immunogenetic analysis of the expression of tumor antigens and responses to tumor antigens” was organized by Dr. T. Hamaoka from Japan and Dr. R. Hodes from the US. There were 19 participants, 11 from the US and 8 from Japan.
This meeting was organized into three primary areas.
I. The Immunology and Molecular Biology of Tumor Antigens.
This series of presentations was focused upon the identification and characterization of tumor-specific antigens and their relation to the transformation event. Dr. Hashimoto first described the characteristics of monoclonal antibodies reactive with a number of human bladder carcinoma lines. These monoclonal antibodies differed in their patterns of reactivity with a series of cell lines and normal tissues. In addition, certain of these antibodies were reactive with extracted glycolipid preparations of cell membranes. It was suggested that the panels of monoclonal antibodies now available might serve as useful diagnostic reagents. Dr. Muramatsu described the structure of embryoglycans, differentiation antigens expressed on embryonal cell carcinomas. He also discussed lectin receptors which were expressed on a number of tissues including embryonal carcinoma cells. Clinical studies have already demonstrated that patient serum levels of embryoglycan are associated with the presence of ovarian germ cell carcinomas and may reflect the course of clinical disease. Dr. Korsmeyer described the study of immunoglobulin gene rearrangements as markers for malignant cells. In a series of human malignancies including hairy cell leukemia, CML. Wiscott-Aldrich, T cell predominant lymphomas, and certain undifferentiated malignancies, efforts were made to study possible relationship to the B cell lineage by examining immunoglobulin gene rearrangements. Such studies have in fact been useful in suggesting the B cell identity of malignancies which are otherwise ambiguous in their expression of cell surface differentiation antigens. Dr. Greene described studies in which transforming genes were isolated from both methylcholanthrene-induced murine tumors and rat neuroblastomas. By transfection studies, it was demonstrated that transforming gene capacity correlated with the ability to induce tumor-specific transplantation antigens. Preliminary studies have suggested the identification and isolation of one glycoprotein which may be related to a transforming gene. The discussion of these presentations centered about the potential diagnostic usefulness of monoclonal antibodies with a high degree of specificity for tumor cells, and upon the important implications of oncogene isolation and the characterization of potential tumor transplantation antigens.
II. The Biology of Host-Tumor Immune Interactions.
The topic of T cell differentiation and regulation was discussed in a series of presentations. Dr. Weissman described the existence of discreet subpopulations of lymphocytes which could be identified on the basis of specific receptors for topographically distinct high walled endothelium. The receptors recognized by these lymphoid subpopulations have been characterized by monoclonal antibodies and tentative isolation of a cDNA clone encoding such a receptor has been made. Dr. Weissman also described studies indicating the clonal origin and maturation of patterns of T cells in the maturing thymus. Dr. Singer described the existence of self MHC restriction in tolerance to non-MHC encoded cell surface determinants. Thus it was found that even in the thymus, tolorance to self “minor antigens” has occurred and is MHC restricted. Dr. Tada described series of T cell-specific anti-Ia reagents. These apparently anti-I-A and anti-I-J reagents were differentially expressed on functional T cell subpopulations, T cell hybridomas, and the antigen specific augmenting and suppressor factors isolated from T cell lines. Studies were described which suggest that these antibodies do not in fact detect I region encoded structural products expressed on the T cell, but rather may identify epitopes on the MHC restricted T cell receptors. Such reagents would thus provide unique and important probes for the analysis of the MHC restricted T cell receptor. Dr. Hodes characterized a regulatory network in which cloned MHC restricted and antigen specific suppressor cells were able to act upon responses mediated by cloned MHC restricted and antigen specific T helper cells. The complex nature of genetic restriction in these systems, as well as the function of additional augmenting or contrasuppressive T cell populations was discussed. These several presentations provided important insights into the complex nature of the developing T cell repertoire, the importance of self MHC restriction in the function of this repertoire, and the mechanisms which are involved in regulation of T cell dependent responses.
Dr. Burakoff has studied the interaction of cytotoxic T cells which target cells employing recent advances in recombinant DNA technology. Recombinant MHC class I genes and recombinant viral genes were employed to dissect the nature of determinants recognized by cytolytic T cells. The spectrum of T cell surface structures which are involved in T cell activation was analyzed by Dr. Fitch. This presentation involved a description of both clonotypic and non-clonotypic reagents, including the newly described anti “L3T4” reagent. The involvement of several of these non clonotypic determinants in antigen recognition by T cells was suggested. Dr. Swain further elaborated upon the critical function of T cell surface determinants involved in recognition of apparently non-polymorphic determinants on class I vs class II MHC products. Dr. Burakoff presented additional data concerning the accessory role of such structures in T cell recognition.
The characterization of lymphokines was the central subject of several additional presentations. Dr. Fitch presented evidence for the ability of multiple lymphokines to produce similar biologic effects and for the ability of individual cloned T cell populations to generate multiple lymphokines. The functional role of interferon and of IL-2 in CTL generation and natural killer function was described by Dr. Kumagai. Dr. Osawa characterized a series of human T cell hybridomas producing multiple lymphokines. Dr. Taniguchi presented extremely exciting information concerning the cloning of genes for human interferon-gamma and IL-2. The nature of the gene structure and existence of enhancing elements involved in regulation of these genes was described.
Dr. Vitetta described the process by which both T cell dependent, antigen specific signals, and alternate signals provided by anti immunoglobulin or B cell mitogens function to drive B cells to activate, proliferate, and differentiate. Dr. Fathrnan described related studies in which it was demonstrated that cloned T helper cells may function in B cell activation through two independent pathways. Dr. Hamaoka summarized recent results in the characterization of B cell receptors for TRF (T cell replacing factor). Monoclonal antibodies against this receptor have allowed preliminary isolation of receptor material and study of its chemical and functional properties. Additional descriptions of B cell growth and differentiation factors were presented by Dr. Dutton and Dr. Swain. Dr. Dutton outlined the existence of at least two forms of B cell growth factor (BCGF). The differential activities of these growth factors in distinct assays of (and potential stages of) B cell activation were described. B cell differentiation factors were similarly analyzed by Dr. Swain. Subsequent discussion of these presentations centered about the apparent complexity of the activation and differentiation signals involved in B cell responses.
III. Preclinical Approaches to Tumor Immunotherapy.
Dr. Osawa described a methodology for coupling the toxin ricin A chain to monoclonal anti-CEA antibody. He was able to demonstrate the selective cytotoxicity of these antibody-toxin conjugates to CEA positive tumor cells in vitro or in Winn assays, but was unable to demonstrate any effective systemic anti tumor activity in other models. The reasons for such limitations were discussed. Dr. Vitetta also described the use of ricin toxins coupled to antibodies. Extensive in vitro and in vivo studies in the BCL1 model demonstrated the ability to generate at least a 5 log kill of idiotype positive tumor cells without detectible anti stem cell effect. A combination of radiation therapy and antibody-toxin immunotherapy was able to produce apparent tumor cures in a majority of experimental animals, although subsequent studies demonstrated the persistance of sub clinical tumor cells in these animals. Dr. Hashimoto employed antibody coated and actinomycin containing liposomes in an anti tumor model. Monoclonal antibody to mouse tumor was employed to target liposomes resulting in cure or inhibition of tumor growth under defined experimental conditions. The T cell subpopulation responsible for tumor rejection in vivo was characterized by Dr. Fujiwara. An immunotherapy protocol involving the generation of hapten-specific helper cells was used to generate anti-tumor T cell populations. It was concluded that Lyt 1+2- T cells mediated this effect. Additional studies in autochthonous tumors suggested that similar protocols of T helper cell dependent anti tumor responses may function in natural tumor settings. The session and meeting were concluded with further consideration of new immunotherapeutic approaches. These approaches were grounded heavily in the basic immunologic and molecular biologic findings of malignant transformation, its relationship to tumor antigenicity, and complex regulation of immune responsiveness.



SEMlNAR AGENDA AND PARTICIPANTS

(1) SEMINAR ON ONCOGENE PRODUCTS AND NEOPLASTIC CELL GROWTH
Washington D.C., October 17- 19, 1983

AGENDA

Monday, October 17, 1983
9 a.m. WELCOMING REMARKS: YOJI IKAWA AND BENOIT DE CROMBRUGGHE
9:00-12:00a.m. SESSION I: Generation of Viral and Cellular Oncogenes
Chairperson: Benoit de Crombrugghe
Transforming Activity of the Src Gene HIDEO IBA
Rockefeller University
Structure and Function of the Oncogenes of some Avian retroviruses KUMAO TOYOSHIMA
University of Tokyo
Structure, Function and Derivation of the Leukemogenic Glycoprotein (GP5 5 ) of the Friend Spleen Focus-forming Virus YOJI IKAWA
Cancer Institute, Tokyo
Institute for Physical and Chemical Research, Wako
Identification of Viral Gene(s) Responsible for the Induction of Erythroleukemia by Friend Murine Leukemia Virus and by Friend Mink Cell Focus Inducing Virus ALAN OLIFF
Memorial Sloan Kettering Cancer Center
2:00-5:00p.m. SESSION II: Mechanisms of Oncogene Activation
Chairperson: Kumao Toyoshima
Expression of the c-myc Gene in Human Tumors SUSAN ASTRIN
Institute for Cancer Research Foxchase Cancer Center
C-myc Gene Amplification in Human Solid Tumors MASABUMI SHIBUYA
University of Tokyo
Chromosome Translocation and Oncogene Activation CARLO CROCE
Wistar Institute
Characterization of p21 RASH Genes
DOUGLAS LOWY
NCI, National Institutes of Health

Tuesday, October 18, 1983
1:00p.m. SESSION III: Cellular Pathways for Transformation :a.m.-
Chairperson: Yoji Ikawa
Transforming growth factor in ASV-transformed rat cells HIROMI MITSUI
Niigata University
Ectopic Release of Regulatory Factors by Transformed Cells and Their Roles in the Expression of the Transformed Phenotype. JOSEPH DeLARCO
NCI, National Institutes of Health
Cell Mutants in Viral Transformation AKIRA HAKURA
Osaka University
Oncogene-specific Cell Factors Analyzed in Cell Fusions MAKOTO NODA
Keio University, Tokyo
The Regulation of Cellular Gene Expression in Transformed Cells ARNOLD LEVINE
Stony Brook
Control of Collagen Gene Expression in Transformed Cells BENOIT DE CROMBRUGGHE
NCI, National Institutes of Health
8:00p.m. Lunch, dinner, free discussions

Wednesday, October 19, 1983
9:00-12:00a.m. SESSION IV: Growth Factors and Cell Surface Receptors: Potential Use for Drug Targeting
Chairperson: Susan Astrin
Structural and Functional Homologies Among the Receptors for Insulin and the Insulin-like Growth Factors MICHAEL CZECH
University of Massachusetts Medical School
Growth Factors Regulate Polyoma Virus Middle T Phosphorylating Activity KAORU SEGAWA
University of Tokyo
Receptor Mediated Oncostatics IRA PASTAN
NCI National Institutes of Health


PARTICIPANTS

UNITED STATES
Dr. Hideo Iba
The Rockefeller University
New York, N.Y. 10021

Dr. Alan Oliff
Memorial Sloan-Kettering Cancer Center
New York, NY 10021

Dr. Susan Astrin
Institute for Cancer Research
The Fox Chase Cancer Center
Philadelphia, PA

Dr. Carlo M. Croce
The Wistar Institute of Anatomy and Biology
Philadelphia, PA

Dr. Douglas R. Lowy
Laboratory of Cellular Oncology
National Cancer Institute
Bethesda, MD 20205

Dr. Joseph E. DeLarco
National Cancer Institute, NIH
Bethesda, MD 20205

Dr. Arnold J. Levine
State University of New York at Stony Brook
School of Medicine, Stony Brook
New York 11794

Dr. Benoit de Crombrugghe
Laboratory of Molecular Biology
National Cancer Institute, NIH
Bethesda, MD 20205

Dr. Michael P. Czech
Department of Biochemistry
University of Massachusetts
Medical School
Worcester, MA 01605

Dr. Ira Pastan
Laboratory of Molecular Biology
National Cancer Institute, NIH
Bethesda, MD 20205

JAPAN
Dr. Kumao Toyoshima
Institute of Medical Science
University of Tokyo
Tokyo 108

Dr. Yoji Ikawa
Laboratory of Molecular Oncology
The Institute of Physical and Chemical Research (RIKEN)
Wako, Saitama 351

Dr. Masabumi Shibuya
The Institute of Medical Science
The University of Tokyo
Tokyo 108

Dr. Hiromi Mitsui
Department of Biology
Faculty of Science
Niigata University
Niigata 950

Dr. Akira Hakura
Research Institute for Microbial Diseases,
Osaka University
Osaka 565

Dr. Makoto Noda
Keio University
Tokyo 160

Dr. Kaoru Segawa
Department of Virology
The Institute of Medical Science
University of Tokyo
Tokyo 108



(2) SEMINAR ON IMMUNOGENETIC ANALYSIS OF THE EXPRESSION OF TUMOR ANTIGENS AND RESPONSES TO TUMORS
San Diego, California, October 31 - November 2, 1983

AGENDA

Monday, October 31
9:00 Introduction
I. The Immunology and Molecular Biology of Tumor Antigens
9:10 Bladder cancer-associated antigens defined with monoclonal antibodies Dr. Yoshiyuki Hashimoto (Tohoku University)
9:50 A role of glycoprotein carbohydrates in antigenicity of tumor cells Dr. Takashi Muramatsu (Kagoshima University)
10:30 Immunoglobulin gene rearrangements as lineage-associated clonal markers Dr. Stanley Korsmeyer (NIH)
11:10 Transformation-related cell surface antigens Dr. Mark Greene (Harvard Medical School)
11:50 Discussion
12:30-2 Lunch
II. The Biology of Host-Tumor Immune Interaction
2:00 Normal and neoplastic maturation of T lymphocytes Dr. Irving Weissman (Stanford University School of Medicine)
2:40 Role of the H-2 complex in T cell tolerance to self antigens Dr. Alfred Singer (NIH)
3:20 Monoclonal antibody recognizing functional receptor on T cells with distinct functions Dr. Tomio Tada (Tokyo University)
4:00 MHC-restricted function of regulatory T cells Dr. Richard Hodes (NIH)
4:40 Discussion

Tuesday, November 1
9:00 Cloned viral and MHC genes as probes of CTL recognition Dr. Steven Burakoff (Sidney Farber Cancer Institute)
9:40 Cell surface structures involved in T cell activation Dr. Frank Fitch (University of Chicago)
10:20 T cell recognition of MHC Dr. Susan Swain (University of California, San Diego)
10:50 Cell surface antigens involved in CTL-target interactions Dr. Steven Burakoff (Sidney Farber Cancer Institute)
11:30 Discussion
12:30-2 Lunch
2:00 Production of lymphokines by cloned murine T cells Dr. Frank Fitch (University of Chicago)
2:40 Role of IFN and IL-2 in CTL generation in vitro and in vivo Dr. Katsuo Kumagai (Tohoku University)
3:20 Human T cell hybridoma producing MIF, MAF , and lymphotoxin
Dr. Toshiaki Osawa (Tokyo University)
3:50 Structure and expression of lymphokine genes Dr. Tadatsugu Taniguchi (Japanese Foundation for Cancer Research)
4:30 Discussion

Wednesday, November 2
9:00 Activation of antigen-specific B cells Dr. Ellen Vitetta (University of Texas Southwestem Medical School)
9:40 Two independent pathways of helper activity from a single T cell clone Dr. C. Garrison Fathman (Stanford University School of Medicine)
10:20 Analysis of TRF-acceptor site on B cells by monoclonal antibody and specific ligand binding Dr. Toshiyuki Hamaoka (Osaka University)
10:50 B cell growth factors Dr. Richard Dutton (University of California, San Diego)
11:30 B cell differentiation factors Dr. Susan Swain (University of California, San Diego)
12:10 Discussion
12:30-2 Lunch
III. Pre-Clinical Approaches to Tumor Immunotherapy
2:00 Anti-tumor activity of monoclonal antibody-ricin A chain conjugates Dr. Toshiaki Osawa (Tokyo University)
2:40 Immunotoxins - an update Dr. Ellen Vitetta (University of Texas Southwestern Medical School)
3:20 T cell subset responsible for rejecting tumor cells in vivo Dr. Hiromi Fujiwara (Osaka University)
4:00 Discussion


PARTICIPANTS

JAPAN
Dr. Hiromi Fujiwara
Institute of Cancer Research
Osaka University Medical School
Osaka, 553

Dr. Toshiyuki Hamaoka
Institute for Cancer Research
Osaka University Medical School
Osaka, 553 Japan

Dr. Yoshiyuki Hashimoto
School of Pharmaceutical Science
Tohoku University
Sendai, 980

Dr. Katsuo Kumagai
Department of Microbiology
Tohoku University School of Dentistry
Sendai, 980

Dr. Takashi Muramatsu
Department of Biochemistry
Kagoshima University
Kagoshima, 890

Dr. Toshiaki Osawa
Division of Chemical Toxicology and Immunochemistry
University of Tokyo
Faculty of Pharmaceutical Sciences Tokyo, 113

Dr. Tomio Tada
Department of Immunology
University of Tokyo
Faculty of Medicine
Tokyo, 113

Dr. Tadatsugu Taniguchi
Japanese Foundation for Cancer Research
Tokyo, 170

UNITED STATES
Dr. Steven J. Burakoff
Dana-Farber Cancer Institute
Boston, Massachusetts 02115

Dr. Richard W. Dutton
Department of Biology
University of California, San Diego
La Jolla, California 92093

Dr. C. Garrison Fathman
Department of Medicine
Stanford University School of Medicine
Stanford, California 94305

Dr. Frank W. Fitch
Department of Pathology
University of Chicago
Chicago, Illinois 60637

Dr. Mark I. Greene
Department of Pathology
Harvard Medical School
Boston, Massachusetts 02115

Dr. Richard J. Hodes
Immunology Branch
National Cancer Institute
National Institutes of Health
Bethesda, Maryland 20205

Dr. Stanley J. Korsmeyer
Metabolism Branch
National Cancer Institute
National Institutes of Health
Bethesda, Maryland 20205

Dr. Alfred Singer
Immunology Branch
National Cancer Institute
National Institutes of Health
Bethesda, Maryland 20205

Dr. Susan L. Swain
Department of Biology
University of California, San Diego
La Jolla, California 92093

Dr. Ellen S. Vitetta
University of Texas Southwestem Medical School at Dallas
Dallas, Texas 75235

Dr. Irving L. Weissman
Department of Pathology
Stanford University School of Medicine
Stanford, California 94305