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ADVANCES IN CANCER RESEARCH VOLUME 46 Interferon Treatment of Human Neoplasia This Page Intentionally Left Blank ADVANCES IN CANCER RESEARCH Edited by GEORGE KLEIN SIDNEY WEINHOUSE Department of Tumor Biology Karolinska lnstitutet Stockholm, Sweden Fels Research Institute Temple University Medical School Philadelphia, Pennsylvania Volume 46 Interferon Treatment of Human Neoplasia By HANS STRANDER Radiumhemmet Karolinska Hospital S-104 01 Stockholm 60, Sweden 1986 ACADEMIC PRESS, INC. Harcourt Brace Jovanovich, Publishers Orlando San Diego New York Austin London Montreal Sydney Tokyo Toronto COPYRIGHT @ 1986 BY ACADEMIC PRESS. INC ALL RIGHTS RESERVED. NO PART OF THIS PUBLICATION MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM OR BY ANY MEANS, ELECTRONIC OR MECHANICAL. INCLUDING PHOTOCOPY. RECORDING, OR ANY INFORMATION STORAGE AND RETRIEVAL SYSTEM. WITHOUT PERMISSION IN WRITING FROM THE PUBLISHER. ACADEMIC PRESS, INC. Orlando. Florida 321187 United Kingdom Edition published by ACADEMIC PRESS INC. ( L O N D O N ) LTD. 24-28 Oval Road. London NWI 7DX LIBRARY OF CONGRESS CATALOG CARD N U M B E R 52-13360 : ISBN 0-12-006646-7 PRINTCD IN THE UNlTtD STATkS (IF AMtHlCA Hh 87 88 89 Y X 7 h S J l ? l CONTENTS PREFACE........................................ ..................... ix Chapter 1. Interferons (IFNs) I . Introduction .................................................. I1. Types ....................................................... 111. Production and Purification ..................................... IV . Induction and Production Control ............................... V . Genetics ..................................................... Chapter 2 . General Action I . Action on Cells in General ..................................... I1 . Action on the Cell Surface ...................................... 111. Tumor Viruses and Oncogenes .................................. IV. Biological Response Modifiers .................................. V . IFNs and Prostaglandins ....................................... 10 15 16 18 19 Chapter 3. Anti-Growth Effects I . The Anti-Growth Concept ...................................... I1 . Anti-Growth Effects in Tissue Culture ............................ 111. Colony Techniques............................................ IV. Theory behind the Anti-Growth Concept ......................... V . Nude Mouse Experiments ...................................... 20 21 28 30 32 Chapter 4 . Effects on the Immune System I. General Effects ............................................... I1. IFNs and NK Cells ............................................ . . 111 Other Effector Systems ........................................ IV Immunoregulatory Circuits ..................................... V 36 44 54 55 vi CONTENTS Chapter 5 . Effects on Other Parameters I . Receptors and Somatic Antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I1. Tumor Cell Antigens and Other Markers .......................... 111. Various Laboratory Parameters .................................. 58 60 61 Chapter 6 . Pharmacology and Toxicity I . IFN Effects in Animals-General Implications .................... I1. Animal Toxici ty ............................................... 111. IFN Titrations and Pharmacokinetics ............................. IV . Anti-IFN Antibodies. .......................................... V. Side Effects and Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . VI . IFN and Disease . . . . . . . . . . . . . . . . .