Investigation and Stimulation of Immunity in Cancer Patients

G.MATHE Institut de Cancerologie et d'Immunogenetique (INSERM et Association Claude-Bernad), H6pital Paul-Brousse and Institute Gustave-Roussy, Villejuif 20 years ago, the main, if not only object of the cancer therapist was to effect complete surgical exeresis or radiotherapeutic destruction of a local tumor, or to obtain, by means of chemotherapy, an "apparently complete regression" of a local or disseminated neoplasia. Today it is realized that (a) at the time of the operation or radiotherapy, two patients in every three carrying an apparently localized tumor have a few cancer cells outside the area where the tumor seems localized; (b) when "apparently complete regression" or even an "apparently complete remission" is induced by chemotherapy, not all the neoplastic cells have been eradicated. In both cases an imperceptible residual neoplasm persists, the growth of which will in due course make it perceptible again, giving rise to metastasis or to a systemic or localized relapse. There is thus an urgent need for a new technique capable of killing the last cell or cells. Our experiments in mice on the effectiveness of active immunotherapy, which involves the manipulation of the immune machinery, have shown that this treatment is able to kill all the cells, down to the very last cell of a given leukemia, provided that the total number of cells does not exceed a few thousand [1, 2].

First Part. Investigation of Immunity in Cancer Patients.- 1. Non Specific.- Selective Activation of T Lymphocytes. Its Possible Application in the Immunomanipulation of Tumours.- Immunological Reactivity of Human Recipients of Syngeneic and Allogeneic Marrow Grafts.- Immunological Studies in Acute Leukemia.- Primary and Secondary Immune Responses in the Evaluation of Immunocompetence and Prognosis in Cancer Patients.- Delayed-Hypersensitivity Reactions in Patients with Cancer.- Nonspecific Immune Responses in Hematosarcomas and Acute Leukemias.- 2. Specific.- Kinetics of Specific Cell-Mediated Immune Response in Cancer-Bearing Hosts.- Technical and Interpretative Problems with Immunofluorescence.- Patterns of Cellular Immunity in Malignant Melanoma.- Lymphocyte-Defined Histocompatibility Differences as a Model for Tumor Antigens.- Cell-Mediated Immunity to Human Solid Tumors: in vitro Detection by Lymphocyte Blastogenic Responses to Cell-Associated and Solubilized Tumor Antigens.- Cell-Mediated and Humoral Immune Response to Acute Leukemia Cells and Soluble Leukemia Antigen-Relationship to Immunocompetence and Prognosis.- Lymphocyte Cytotoxicity in Human Acute Leukemia.- Lymphocyte-Mediated Cytotoxicity and Tumor Immunity.- Cell-Mediated Immunity in Allogeneic and Tumor-Systems: Nature of the Cells Involved in Killing Target Cells.- Inhibition of Leukocyte Migration in Man.- Effect of Autologous Serum on in vitro Inhibition of Leukocyte Migration by Autochthonous Tumor Extracts from Human Patients.- Serum Inhibitory Factors in Acute Leukemia.- Delayed Hypersensitivity Response toward Autochthonous Tumor Extracts.- Second Part. Stimulation of Immunity and Cancer Immunity.- 1. Experimental.- Experimental Screening for “Systemic Adjuvants of Immunity” Applicable in Cancer Immunotherapy.- Experimental Screening of Systemic Adjuvants Extracted from Mycobacteria.- Chemical Structure of Mycobacterial Cell Walls.- Water-Soluble, ImmunoAdjuvants form the Cell Wall of Mycobacterium Smegmatis.- Stimulation of T Cell Activity by a Methanol-Extraction Residue (MER) of BCG.- Biological Properties of Non-Toxic Water-Soluble Immunoadjuvants from Mycobacterial Cells.- Enhancement of Human Mixed-Lymphocyte Cultures by a Water-Soluble Adjuvant.- Early Recovery of the Immune Response of a Specifically Depleted Cell Population under the Influence of Water-Soluble Adjuvant.- An Adjuvant-Active Water-Soluble Substance (“Polysaccharide-Peptidoglycan”) from Mycobacterial Cells. Preparation by a Simple Extraction Technique.- MAAF: A Fully Water-Soluble Lipid-Free Fraction from BCG with Adjuvant and Antitumor Activity.- Comparative Study of the Free Lipids of Eight BCG Daughter Strains.- A Galactose Disaccharide from Immunoadjuvant Fractions of Mycobacterium Tuberculosis (Cell Wall and Wax D).- Summary of Working Session on the Mechanism of Action of Immunological Adjuvants.- BCG and the Lympho-Reticuloendothelial System.- Effect of Corynebacterium Parvum on Resistance to Experimental Leukemia in Relation to Genetic Modification of Immunoresponsiveness.- The Influence of Mycobacterium Bovis and Corynebacterium Parvum on the Phospholipid Metabolism of Macrophages.- Separation and Purification of Cord Factor (6,6?-Dimycoloyl Trehalose) from Wax C or from Mycolic Acids.- Granuloma Induction and Stimulation of the Immune Response in Mice with Trehalose-6,6?-Dimycolate.- Corynebacterium Parvum: An Immunomodulator.- Nonspecific Effects of Corynebacteria on Systemic Immunity Responses.- Immunostimulating Activity of Whole Cells, Cell-Walls and Fractions of Anaerobic Corynebacteria.- Nonspecific Stimulation by Inactivated or Ultrasonicated Brucella Abortus.- Increase of Brucella-Induced Immunostimulation by Administration in Combination with a Specific Antiserum.- Alterations in Immune Response to Experimental Murine Tumor-Associated Antigens Following Administration of BCG or Polysaccharide from Proteus vulgaris.- Cell-Mediated Immunity in AKR Mice Treated with Lentinan, a Fungal Polysaccharide.- The Antitumor Effects of Interferon.- Use of Double-Stranded Synthetic Polynucleotides in Amplifying Immunologically Induced Lymphocyte Proliferation.- Immunoenhancing and Antitumor Effects of Agents that Elevate Endogenous Cyclic AMP Levels.- BCG Immunotherapy of Pulmonary Deposits from Experimental Rat Tumours of Defined Immunogenicity.- Specific and Nonspecific Immunotherapy: Use of BCG.- Poly A. Poly U as an Adjunct to Surgery in the Treatment of Spontaneous Murine Mammary Adenocarcinoma.- Combined Chemotherapy and Immunotherapy of Transplantable and Spontaneous Murine Leukemia in DBA/2 and AKR Mice.- Modification of Immunogenicity in Experimental Immunotherapy and Prophylaxis.- Aspects of the Immunology of the Tumor-Host Relationship and Responsiveness to Modified Lymphoma Cells.- Use of Enzyme-Treated Cells in Immunotherapy of Leukemia.- Active Immunotherapy of AKR Mouse Spontaneous Leukemia.- Augmented Immunogenicity of Tumor Cell Homogenates Infected with Influenza Virus.- Characterization and Purification of Rauscher Leukemia-Associated Transplantation Antigens.- The in vivo Activity of Soluble Extracts Obtained from RC19 Leukemia: Effect of the Method of Extraction.- The Preferential Induction of Cell-Mediated Immunity and Some Preliminary Observations on its Application to Tumor Immunotherapy.- 2. Clinical.- Clinical Screening of Systemic Adjuvants of Immunity.- BCG Vaccination and Leukemia Mortality.- Immunologic Effects of BCG in Patients with Malignant Melanoma.- Attempts at Immunotherapy of 100 Acute Lymphoid Leukemia Patients: Some Factors Influencing Results.- Immunotherapy of Acute Myeloblastic Leukemia in Man.- Acute Myeloblastic Leukemia: Replication of Avian Influenza Virus in Human Myeloblasts and First Attempt at Clinical Application.- Preliminary Results of a Randomized Trial of BCG Immunotherapy in Burkitt’s Lymphoma.- BCG Immunotherapy in the Treatment of Inoperable Carcinoma of the Lung.- Effect of BCG Stimulation on the Growth Rate of Pulmonary Metastases in 3 Patients with Melanoma.- Immunotherapy of a Solid Tumor (Melanoma) with BCG: A Comment on the Risks of Enhancement.- BCG Stimulation of Immune Responsiveness in Patients with Malignant Melanoma.- Clinical Results with Corynebacteria.- A Clinical Trial of Autogenous Vaccines in the Treatment of Osteogenic Sarcoma.- Immunization with Cultured Cell-BCG Mixtures.