Investigation and Stimulation of Immunity in Cancer Patients

508 Pages·1974·22.768 MB·English

by  G. Mathé (auth.), Georges Mathé, Roy Weiner M.D. (eds.)

Recent Results in Cancer Research
Fortschritte der Krebsforschung
Progd:s dans Ies recherches sur Ie cancer
47
Edited by
V. G. AllJrey, New York· M. Allgower, Basel· K. H. Bauer, Heidelberg
1. Berenblum, Rehovoth . F. Bergel, Jersey· J. Bernard, Paris
W. Bernhard, VillejuiJ . N. N. Blokhin, Moskva' H. E. Bock, Tubingen
P. Bucalossi, Milano' A. V. Chaklin, Moskva
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Editor in CieJ
P. Rentchnick, Geneve
Investigation and Stimulation
of Immunity in Cancer Patients
Edited by
G. Mathe and R. Weiner
With 143 Figures
Springer-Verlag Berlin· Heidelberg. New York 1974
Proceedings of the CNRS Colloquium. Paris, June 21-22,1972
GEORGES MATHE, Professor, Institut de Cancerologie et d'Immunogenetique,
H6pital Paul-Brousse, F-94 Villejuif
Roy WEINER, M.D., Children's Cancer Research Foundation,
35 Binney Street, Boston, MA 02115/USA
Sponsored by the Swiss League against Cancer
Library of Congress Cataloging in Publication Data
Main entry under title:
Investigation and stimulation of immunity in cancer patients.
(Recent results in cancer research, 47)
"Proceedings of the CNRS colloquium, Paris, June 21-22, 1972 ... Sponsored by the Swiss
League against Cancer."
Bibliography: p.
1. Cancer-Immunological aspects. 1. Mathe, Georges, 1922- ed. II. Weiner, Roy S., ed. III.
France. Centre national de la recherche scientifique. IV. Schweizerische Nationalliga fiir
Krebsbekampfung und Krebsforschung. V. Series.
RC261.R35 no. 47 [RC262] 616.9'94'008s [616.9'94'079] 74-10816
ISBN 978-3-642-49286-0 ISBN 978-3-642-49284-6 (eBook)
DOI 10.1007/978-3-642-49284-6
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Contents
Introduction . 1
First Part. Investigation of Immunity in Cancer Patients
1. Non Specific
MILLER, J. F. A. P.: Selective Activation of T Lymphocytes. Its Possible Appli-
cation in the Immunomanipulation of Tumours. 5
THOMAS, E. D., FASS, 1., OCHS, H. D., MICKELSON, E. M., STORB, R., FEFER, A.:
Immunological Reactivity of Human Recipients of Syngeneic and Alloge-
neic Marrow Grafts . 12
SANTOS, G. W., MULLINS, G. M., BIAS, W. B., ANDERSON, P. N., GRAZIANO,
K. D., KLEIN, D. 1., BURKE, P. ].: Immunological Studies in Acute Leu-
kemia . 17
HERSH, E. M., FREIREICH, E. ]., MCCREDIE, K. B., GUTTERMAN, J. U., BODEY,
G. P., WHITECAR, J. P., MAVLIGIT, G., CHEEMA, A. R.: Primary and Sec
ondary Immune Responses in the Evaluation of Immunocompetence and
Prognosis in Cancer Patients . . . . . . . . . 25
PINSKY, C. M., EL DOMEIRI, A., CARON, A. S., KNAPPER, W. H., OETTGEN, H. F.:
Delayed-Hypersensitivity Reactions in Patients with Cancer . 37
SCHNEIDER, M., MATHE, G., SCHWARZENBERG, 1., POUILLART, P., WEINER, R.,
AMIEL, J. 1., HAYAT, M., JASMIN, C., DE VASSAL, F.: Nonspecific Immune
Responses in Hematosarcomas and Acute Leukemias . . • . 42
2. Specific
BARSKI, G., YOUN, J. K., LE FRANCOIS, D.: Kinetics of Specific Cell-Mediated
Immune Response in Cancer-Bearing Hosts . . . . . . . . . . • 54
LEWIS, M. G.: Technical and Interpretative Problems with Immunofluorescence 58
CLARK, D. A., NATHANSON, 1.: Patterns of Cellular Immunity in Malignant
Melanoma . . . . . • . • • 67
WIDMER, M. B., SEGALL, M., BACH, F. H., BACH, M. 1.: Lymphocyte-Defined
Histocompatibility Differences as a Model for Tumor Antigens. . . . . 79
MAVLIGIT, G. M., GUTTERMAN, J. U., McBRIDE, CH. M., HERSH, M. E.: Cell
Mediated Immunity to Human Solid Tumors: in vitro Detection by Lympho
cyte Blastogenic Responses to Cell-Associated and Solubilized Tumor
Antigens . ....... .••..•... 84
VI Contents
GUTTERMAN, J. D., HERSH, E. M., MAVLIGIT, G., FREIREICH, E. J., ROSSEN,
R. D., BUTLER, W. T., MCCREDIE, K. B., BODEY, G. P., RODRIGUEZ, V.: Cell
Mediated and Humoral Immune Response to Acute Leukemia Cells and
Soluble Leukemia Antigen-Relationship to Immunocompetence and Prog-
noSIS . 97
LEVENTHAL, B. G., HALTERMAN, R. H., ROSENBERG, E. B., McCoy, J. L.,
HERBERMAN, R. B.: Lymphocyte Cytotoxicity in Human Acute Leukemia. 113
CEROTTINI, J.-c.: Lymphocyte-Mediated Cytotoxicity and Tumor Immunity. 118
LECLERC, J. c., LEVY, J. P., GOMARD, E., PLATA, F., KOURILSKY, F. M.: Cell
Mediated Immunity in Allogeneic and Tumor-Systems: Nature of the Cells
Involved in Killing Target Cells . 122
REMOLD, H. G.: Inhibition of Leukocyte Migration in Man . 127
LACOUR, F., LACOUR, J., SPIRA, A., BAYET, S.: Effect of Autologous Serum on
in vitro Inhibition of Leukocyte Migration by Autochthonous Tumor Ex-
tracts from Human Patients 129
FREEMAN, C. B., WALKER, J. S., DAVIEs, D., COCKING, H., HARRIS, R.: Serum
Inhibitory Factors in Acute Leukemia . 133
HERBERMAN, R. B.: Delayed Hypersensitivity Response toward Autochthonous
Tumor Extracts 140
Second Part. Stimulation of Immunity and Cancer Immunity
1. Experimental
MATHE, G., KAMEL, M., DEZFULIAN, M., HALLE-PANNENKO, 0., BOURUT, c.:
Experimental Screening for "Systemic Adjuvants of Immunity" Applicable
in Cancer Immunotherapy . 149
CHEDID, L., LAMENSANS, A.: Experimental Screening of Systemic Adjuvants
Extracted from Mycobacteria. 166
PETIT, J. F., ADAM, A., CIORBARU, R., WIETZERBIN-FALSZPAN, J., LEDERER, E.:
Chemical Structure of Mycobacterial Cell Walls . . 173
ADAM, A., CIORBARU, R., PETIT, J. F., LEDERER, E.: Water-Soluble, Immuno-
Adjuvants form the Cell Wall of Mycobacterium Smegma tis . 179
JACOBS, D., YASHPHE, D. J., ABRAHAM, c.: Stimulation of T Cell Activity by a
Methanol-Extraction Residue (MER) of BCG 183
PARANT, M., CHEDID, L.: Biological Properties of Non-Toxic Water-Soluble
Immunoadjuvants from Mycobacterial Cells . 190
BONA, c., HEUCLIN, c., CHEDID, L.: Enhancement of Human Mixed-Lympho-
cyte Cultures by a Water-Soluble Adjuvant. 196
LIACOPOULOS, P., BIRRIEN, J. L., BLEUX, c., COUDERC, J.: Early Recovery of
the Immune Response of a Specifically Depleted Cell Population under the
Influence of Water-Soluble Adjuvant . 201
MIGLIORE-SAM OUR, D., JOLLEs, P.: An Adjuvant-Active Water-Soluble Sub
stance ("Polysaccharide-Peptidoglycan") from Mycobacterial Cells. Pre-
paration by a Simple Extraction Technique . 207
Contents VII
Hru, I. J.: MAAF: A Fully Water-Soluble Lipid-Free Fraction from BeG with
Adjuvant and Antitumor Activity • 213
ASSELINEAU, J., PORTELANCE, V.: Comparative Study of the Free Lipids of
Eight BCG Daughter Strains . 214
VILKAS, E., AMAR-NAcAscH, c., MARKOVITS, J.: A Galactose Disacmaride from
Immunoadjuvant Fractions of Mycobacterium Tuberculosis (Cell Wall and
Wax D) . 221
BENACERRAF, B.: Summary of Working Session on the Mechanism of Action of
Immunological Adjuvants . . • . . . . . . . 224
ROSENTHAL, S. R.: BCG and the Lympho-Reticuloendothelial System. 228
STIFFEL, C., MOUTON, D., BIOZZI, G.: Effect of Corynebacterium Parvum on
Resistance to Experimental Leukemia in Relation to Genetic Modification
of Immunoresponsiveness • . . . . • • . . • • • . . 239
MUNDER, P. G., MODoLELL, M.: The Influence of Mycobacterium Bovis and
Corynebacterium Parvum on the Phospholipid Metabolism of Macrophages 244
GOREN, M. B., BRoKL, 0.: Separation and Purification of Cord Factor (6,6'~Di­
mycoloyl Trehalose) from Wax C or from Mycolic Acids. . . . . . . 251
BEKIERKUNST, A.: Granuloma Induction and Stimulation of the Immune Re-
sponse in Mice with Trehalose-6,6'-Dimycolate. .... 259
HALPERN, B.: Corynebacterium Parvum: An Immunomodulator . 262
WOODRUFF, M. F. A.: Nonspecific Effects of Corynebacteria on Systemic Im
munity Responses . 272
J.-c.,
KOUZNETZOVA, B., BIZZINI, B., CHERMANN, DEGRAND, F., PREVOT, A.-R.,
RAYNAUD, M.: Immunostimulating Activity of Whole Cells, Cell-Walls and
Fractions of Anaerobic Corynebacteria. . .. .... 275
PILET, CH., LE GARREC, Y., TouJAs, L., SABOLOVIC, D., MONTEIL, J. C.,
J.:
ROTHIER, F., MISHRA, U., GHEBREIDWET, B., GUELFI, Nonspecific Stimu
lation by Inactivated or Ultrasonicated Brucella Abortus. . . 294
TouJAs, L., DAzoRD, L., GUELFI, J.: Increase of Brucella-Induced Immuno
stimulation by Administration in Combination with a Specific Antiserum • 302
DONNER, M., VAILLIER, D.: Alterations in Immune Response to Experimental
Murine Tumor-Associated Antigens Following Administration of BCG or
Polysacmaride from Proteus vulgaris . . . . . 308
c.,
BORTIN, M. M., RIMM, A. A., SALTZSTEIN, E. SHALABY, M. R., RODEY, G. E.:
Cell-Mediated Immunity in AKR Mice Treated with Lentinan, a Fungal
Polysaccharide. . . • . . . . . 320
GRESSER, I.: The Antitumor Effects of Interferon 327
MARDINEY, M. R., CHESS, L., LEVY, C., SCHMUKLER, M., SMITH, K.: Use of
Double-Stranded Synthetic Polynucleotides in Amplifying Immunologically
Induced Lymphocyte Proliferation . • • . • • . 330
c.:
BRAUN, W., SHIOZAWA, Immunoenhancing and Antitumor Effects of Agents
that Elevate Endogenous Cyclic AMP Levels . ..•.... 338
BALDWIN, R. W., PIMM, M. V.: BCG Immunotherapy of Pulmonary Deposits
from Experimental Rat Tumours of Defined Immunogenicity • 345
ZBAR, B.: Specific and Nonspecific Immunotherapy: Use of BCG . 350
VIII Contents
LACOUR, F., LACOUR, J., SPIRA, A.: Poly A. Poly U as an Adjunct to Surgery
in the Treatment of Spontaneous Murine Mammary Adenocarcinoma. 352
BEKESI, J. G., HOLLAND, J. F.: Combined Chemotherapy and Immunotherapy
of Transplantable and Spontaneous Murine Leukemia in DBA/2 and AKR
Mice . 357
SIMMONS, L. R., RIDS, A.: Modification of Immunogenicity in Experimental
Immunotherapy and Prophylaxis. 370
PRAGER, M. D., RIBBLE, R. ]., MEHTA, ]. M.: Aspects of the Immunology of the
Tumor-Host Relationship and Responsiveness to Modified Lymphoma Cells 379
c.,
DORE, J. F., HADJIYANNAKIS, M. ]., COUDERT, A., GUIBOUT, MARHOLEY, 1.,
IMAI, K.: Use of Enzyme-Treated Cells in Immunotherapy of Leukemia. 387
c.:
MATHE, G., HALLE-PANNENKO, 0., BOURUT, Active Immunotherapy of
AKR Mouse Spontaneous Leukemia. 389
BOONE, C. W.: Augmented Immunogenicity of Tumor Cell Homogenates In-
fected with Influenza Virus. 394
MARTYRE, M.-C., HALLE-PANNENKO, 0., JOLLES, P.: Characterization and Puri-
fication of Rauscher Leukemia-Associated Transplantation Antigens. 401
MARTYRE, M.-C., WEINER, R., HALLE-PANNENKO, 0.: The in vivo Activity of
Soluble Extracts Obtained from RC19 Leukemia: Effect of the Method
of Extraction . 405
BENJAMINI, E., SCIBIENSKI, R. T.: The Preferential Induction of Cell-Mediated
Immunity and Some Preliminary Observations on its Application to Tumor
Immunotherapy 408
2. Clinical
BLUMING, A., VOGEL, L., ZIEGLER, ]. L.: Clinical Screening of Systemic Adju-
vants of Immunity 415
ROSENTHAL, S. R., CRISPEN, R. G., THORNE, M. G., PIEKARSKI, N., RAISYS, N.,
RETTIG, P.: BCG Vaccination and Leukemia Mortality 421
c.,
MARDINEY, M. R., CHESS, 1., BOCK, G. N., UNGARO, P. BUCHHOLZ, D. H.:
Immunologic Effects of BCG in Patients with Malignant Melanoma . 426
MATHE, G., POUILLART, P., SCHWARZENBERG, 1., WEINER, R., RAPPAPORT, H.,
c.,
HAYAT, M., DE VASSAL, F., AMIEL, J. L., SCHNEIDER, M., JASMIN, ROSEN
c.:
FELD, Attempts at Immunotherapy of 100 Acute Lymphoid Leukemia
Patients: Some Factors Influencing Results . 434
POWLES, R., McELMAIN, T. ]., ALEXANDER, P., CROWTHER, D., FAIRLEY, G.,
PIKE, M.: Immunotherapy of Acute Myeloblastic Leukemia in Man. 449
c.,
SAUTER, LINDENMANN, ]., GERBER, A., MARTZ, G.: Acute Myeloblastic
Leukemia: Replication of Avian Influenza Virus in Human Myeloblasts and
First Attempt at Clinical Application . 455
MAGRATH, I. T., ZIEGLER, J. 1., BLUMING, A. Z.: Preliminary Results of a Ran-
domized Trial of BCG Immunotherapy in Burkitt's Lymphoma . 461
PINES, A.: BCG Immunotherapy in the Treatment of Inoperable Carcinoma of
the Lung . 466
Contents IX
RUMKE, P., BERNHEIM, J., V. D. VORM, D. H., VAN PEPERZEEL, H. A., Looy
SEN, R.: Effect of BCG Stimulation on the Growth Rate of Pulmonary
Metastases in 3 Patients with Melanoma. 470
BERNHEIM, J. J. L.: Immunotherapy of a Solid Tumor (Melanoma) with BCG:
A Comment on the Risks of Enhancement 473
GUTTERMAN, J. D., MAVLIGIT, G., McBRIDE, CH. M., FREI, E. III, HERSH, E. M.:
BCG Stimulation of Immune Responsiveness m Patients with Malignant
Melanoma 476
ISRAEL, L.: Clinical Results with Corynebacteria. 486
c.:
MARCOVE, R. A Clinical Trial of Autogenous Vaccines in the Treatment of
Osteogenic Sarcoma . 488
SOKAL, J. E., AUNGST, C. W.: Immunization with Cultured Cell-BCG Mixtures 496
Introduction
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].
We proposed in 1964 to use active immunotherapy to eradicate the residual cells
left by chemoradiotherapy in acute lymphoid leukemia (ALL). Seven of the 20 patients
randomized in the immunotherapy group are still in remission today and have not
presented with a relapse for periods varying from 7 to 10 years. On the other hand,
all. the controls relapsed within a few months. This is indeed a demonstration of the
ability of immunotherapy to eradicate the last cells [3,4].
The evidence is accumulating: our other trials on ALL [4, 5], our trial on leu
kemic (terminal) lymphosarcomas [5], those of POWLES in the U.K. [6] and of the
South Eastern Group in the U.S.A. [7] on acute myeloid leukemia, Sokal's trials
on chronic myeloid leukemia [8] and on non leukemic lymphomas [9], BLUMING'S
trial [10], and the trial of GUTTERMAN, HERSCH, FREIREICH and FREI on melanoma
[11], and now that of MARCOVE and SOUTHAM [12] on osteosarcoma demonstrate
that immunotherapy acts on the imperceptible residual disease.
Another approach to active immunotherapy, called "local" because of the intra
tumor administration of the immunity-manipulating agents, has been tried with
success by ZBAR and RAPP [13] in guinea pigs, and by MORTON et al. [14] in man.
2 G. MATHE: Introduction
Active immunotherapy [15], complementing the adoptive immunotherapy
proposed by us in 1959 [16], and passive immunotherapy [17], is now the fourth
method of treating cancer. The time is now ripe for it to be used in an attempt to
eradicate the imperceptible residual disease left by the surgeon, the radiotherapist,
or the chemotherapist.
For this treatment to succeed, progress must be made not only in the techniques
and methods of active immunotherapy, but also in evaluating the immune status
of the patient. And finally, there is still room for improvement in the logistics of
treating cancer patients.
References
1. MATHE, G.: Immunotherapie active de la leucemie L 1210 appliquee apres la greffe tumorale.
Rev. Fr. Et. Clin. BioI. 13, 881 (1968).
2. MATHE, G., POUILLART, P., LAPEYRAQUE, F.: Active immunotherapy ofL 1210 leukemia applied
after the graft of tumour cells. Brit. J. Cancer 23, 814 (1969).
3. MATHE, G., AMIEL, J. L., SCHWARZENBERG, L., SCHNEIDER, M., CATTAN, A., SCHLUMBERGER,
J. R., HAYAT, M., DE VASSAL, P.: Active immunotherapy for acute lymphoid leukemia. Lancet
1969 1,697.
4. MATHE, G., SCHWARZENBERG, L., AMIEL, J. L., POUILLART, P., HAYAT, M., DE VASSAL, F.,
c., c.:
ROSENFELD, JASMIN, New experimental and clinical data on leukemia immunotherapy.
Proc. Royal Soc. Med. 1974, in press.
5. MATHE, G., POUILLART, P., SCHWARZENBERG, L., HAYAT, M., AMIEL, J. L., DE VASSAL, F.:
Leukaemic conversion of non-Hodgkin's malignant lymphomas. Brit. J. Cancer 1974, in press.
6. POWLES, R., KAY, H. E. M., McELWAIN, T. J., ALEXANDER, P., CROWTHER, D., HAMILTON
FAIRLEY, G., PIKE, M.: Immunotherapy of acute myeloblastic leukaemia in man. In: Investiga
tion and stimulation of immunity in cancer patients (G. MATHE and R. WEINER, Eds.). Berlin
Heidelberg-New York: Springer 1974.
7. VOGLER, W. R., CHAN, Y. K.: Effect of bacillus-Calmette Guerin (BCG) in prolongation of
remissions in acute myeloblastic leukemia (AML). Proc. Amer. Ass. Cancer Res. 15, 164 (1974).
(Abstract no. 723.)
8. SOKAL, J. E., AUNGST, C. W.: Immunization with cultured cell-BCG mixtures. In: Investigation
and stimulation of immunity in cancer patients (G. MATHE and R. WEINER, Eds.). Berlin
Heidelberg-New York: Springer 1974.
9. SOKAL, J. E., AUNGST, C. W., SNYDERMAN, M.: Prolongation of remission in stage I and II
lymphoma by BCG vaccination. Proc. Amer. Ass. Cancer Res. 15, 13 (1974). (Abstract no. 51.)
10. BLUMING, A. Z., VOGEL, C. L., ZIEGLER, J. L., MODY, N., KAMYA, G.: Immunological effects
of BCG in patients with malignant melanoma. A comparison of two modes of administration.
Ann. Intern. Med. 76, 405 (1972).
11. GUTTERMAN, J. D., McBRIDE, c., PREIREICH, E. J., MAVLIGIT, G., FREI, E. III, HERSH, E. M.:
Active immunotherapy with BCG for recurrent malignant melanoma. Lancet 1973 I, 1208.
c.,
12. MARCOVE, R. SOUTHAM, C. M., LEVIN, A. G., HUVORS, A. G., MIKE, V.: A clinical trial of
autogenous vaccine in the treatment of osteogenic sarcoma. In: Investigation and stimulation of
immunity in cancer patients (G. MATHE and R. WEINER, Eds.). Berlin-Heidelberg-New York:
Springer 1974.
13. ZBAR, B., BERNSTEIN, 1. D., RAPP, H. J.: Suppression of tumor growth at the site of infection
with living bacillus Calmette-Guerin. J. Nat. Cancer Inst. 46, 831 (1971).
14. MORTON, D. L., EILBER, F. R., MALMGREN, R. A., WOOD, W. C.: Immunological factors which
influence response to immunotherapy in malignant melanomas. Surgery 68, 158 (1970).
15. MATHE, G.: Active immunotherapy. Adv. Cancer Res. 14, 1 (1971).
16. THOMPSON, R. B., MATHE, G.: Adoptive immunotherapy in malignant disease. Transplant Rev.
9, 54 (1972).
17. MOTTA, R.: Passive immunotherapy of leukemia and other cancers. Adv. Cancer Res. 14, 161
(1971).