In Vitro Evaluation of Macrophage Mediated Host Defenses against Neoplastic Disease

  • R. Kirsh
  • P. J. Bugelski
Part of the NATO ASI Series book series (NSSA, volume 218)


The ability of malignant tumors to disseminate to organs distant from the site of the primary lesions is the principal reason for failure in cancer therapy.(1) There are several reasons for this high failure rate. First, at the time of initial diagnosis, metastatic lesions may be too small to detect using currently available diagnostic methodologies; second, the anatomic location of the metastatic lesion may limit the dose of antineoplastic drug that can reach the site without excessive toxicity; and third, the heterogeniety of tumor cell phenotypes within a single lesion is sufficiently diverse, that the responsiveness of cells from one lesion to an antineoplastic modality can differ from both the primary lesion and other metastases.(2–4) This latter issue suggests that the development of an effective therapy for metastatic disease approaches that will circumvent the problems of cellular heterogenicity.


Alveolar Macrophage Human Monocyte Macrophage Activation Mouse Macrophage Macrophage Population 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Poste, G. and Fidler, I.J., The pathogenesis of cancer metastasis. Nature (London), 283, 139, 1980.CrossRefGoogle Scholar
  2. 2.
    Poste, G. and Greig, R., On the genesis and regulation of cellular heterogeneity in malignant tumors, Invasion and Metastasis, 2, 137, 1982.Google Scholar
  3. 3.
    Kerbel, R.S., Implications of immunological heterogeneity of tumors, Nature (London), 280, 358, 1979.CrossRefGoogle Scholar
  4. 4.
    Owens, A.H., Coffey, D.S., and Baylin, S.B., Eds., in Tumor Cell Heterogeneity: Origins and Implications. Academic Press, New York, 1982.Google Scholar
  5. 5.
    Eccles, S.A., Macrophages and cancer, in Immunological Aspects of Cancer, Castro, J.E., Ed., University Park Press, Baltimore, 1978, 123.CrossRefGoogle Scholar
  6. 6.
    Chirigos, M.A., Mitchell, M., Mastrangelo, M.J., and Krim, M., Eds., Modulation of Cellular Immunity in Cancer by Immune Modifiers, Raven Press, New York, 1981.Google Scholar
  7. 7.
    Witz, I.P. and Hanna, M.G., Jr., Eds., In situ expression of tumor ummunicty, Contemp. Top. Immunobiol., 10, 1, 1980.PubMedGoogle Scholar
  8. 8.
    Mantovani, A., Giavazzi, R., Polentaniti, N., Spreafico, F., and Garanttini, S., Divergent effects of macrophage toxins on growth primary tumors and lung metastases in mice, Int. J. Cancer, 25, 617, 1980.PubMedCrossRefGoogle Scholar
  9. 9.
    Fidler, I.J., and Poste, G., Macrophage-mediated destruction of malignant tumor cells and new sstrategies for the therapy of metabolic disease, Springer Semin. Immunopathol., 5. 161, 1982.PubMedCrossRefGoogle Scholar
  10. 10.
    Poste, G., and Kirsh, R. (1982). Liposome-encapsulated macrophage activation agents and active non-specific immunotherapy of neoplastic disease. In “Cell Function and Differentiation” G.A. Koyunoglou, A.E. Evangelopoulos, J. Georgatsos, G. Palarologos, A. Trakatellis, and C.P. Tsiganos, eds., 309–319, Alan R. Liss, New York.Google Scholar
  11. 11.
    Trope, C., Different susceptibilities of tumor cell subpopulations to cytotoxic agents, in Design of Models for Testing Cancer Chemotherapeutic Agents, Fidler, I.J. and White, R.J., Eds., Van Nostrand, New York, 1982, 64.Google Scholar
  12. 12.
    Colotta, R., Peri, G., Villa A. and Mantovani Rapid killing of actinoiycen D treated tumor cells by human mononuclear cells. J. Immunol., 132, 936, 1984.PubMedGoogle Scholar
  13. 13.
    North, R.J., The concept of activated macrophages, J. Ummunol., 121, 806, 1978.Google Scholar
  14. 14.
    Hanna, N., Role of natural killer cells in control of cancer metastasis, Cancer Metastasis Rev., 1, 45, 1982.PubMedCrossRefGoogle Scholar
  15. 15.
    Alexander, P. and Evans, R., Endotoxin and double stranded RNA render macrophages cytotoxic, Nature (London). 232, 76, 1971.Google Scholar
  16. 16.
    Adams, D.O. and Hamilton, T.A., The cell biology of macrophage activation, Annu. Rev. Immunol., 2, 283, 1984.PubMedCrossRefGoogle Scholar
  17. 17.
    Nathan, CF. and Cohn, Z.A., Cellular components of inflammation: monocytes and macrophages, in Textbook of Pheumatology, Kelley, W., Harris, E., Ruddy, S., and Sledge, Cl., Eds., W.B. Saunders, Philadelphia, 1985, 144.Google Scholar
  18. 18.
    Takemura, R. and Werb, Z., Secretory products of macrophages and their physiological functions, Am. J. Physiol. 246, Cl. 1984.Google Scholar
  19. 19.
    Gordon, S. and Hirsch, S., Differntiation antigens and macrophage heterogencity, in Macrophages and Natural Killer Cells, Norman, S. and Sorkin, E., Eds., Plenum Press, New Yoark, 1982, 391.CrossRefGoogle Scholar
  20. 20.
    Walker, W.S., Functional heterogencity of macrophages, in Immunobiology of the Macrophage, Nelson, D., Ed., Academic Press, Orlando, Fla. 1986, 91.Google Scholar
  21. 21.
    Adams, D.O. and Marino, P.A., Activation of mononuclear phagocytes for destruction of tumor cells as a model for sutdy of macrophage development, in Contemporary Topics in Hematology-Onocology, Gordon. A., Stiber, R., and LoBue, J., Eds., Plenum Press, New York, 1984, 69.Google Scholar
  22. 22.
    Fischer, D.G., Hubbard, W.J., and Koren, H.S., Tumor cell killing by freshly isolated peripheral blood monocytes, Cell. Immunol., 58, 426, 1981.PubMedCrossRefGoogle Scholar
  23. 23.
    Johnson, W.J., Marino, P.A., Schrieber, R.D., and Adams, D.O., Sequential activation of murine mononuclear phagocytes for tumor cyutolysis: differential expresion of markers by macrohages in the several stages of development, J. Ummunol., 131, 1038, 1983.Google Scholar
  24. 24.
    Johnson, W.J., Di Martino, M.J., and Hanna, J., Macrophage activation in rat models of inflammation and athritis: determination of markers of stages of activation, Cell. Immunol., 103, 54, 1986.PubMedCrossRefGoogle Scholar
  25. 25.
    Pace, J.L., Varesio, J., Russell, S.W., and Blasi, E., The strain of mouse and assay conditions influence whether nuLFN-γ primes or activates macrophages for tumor killing, J. Leukocyte Biol., 37, 475, 1985.PubMedGoogle Scholar
  26. 26.
    Murray, H.W., Spitainy, G.L., and Nathan, CF., Activation of mouse peritoneal macrophages in vitro and in vivo by interferon-γ, J. Immunol., 138, 491, 1987.Google Scholar
  27. 27.
    Black, CM., Catterall, J.R., and Remington, J.S., In vivo and in vitro activation of alveolar macrophages by recombinant interferon-y, J. Immunol., 138, 491, 1987.PubMedGoogle Scholar
  28. 28.
    Lehrer, R.I., Ferrari, L.G., Patterson-Delafield, J., and Sorrell, T., Fungicidal activity of rabbit alveolar and peritoneal macrophages against Candida albicans, Infect. Immun., 28, 1001, 1980.PubMedGoogle Scholar
  29. 29.
    Collins, F.M., Niederbuhl, C J., and Campbell, S.G., Bactericidal activity of alveolar and peritoneal macrophages exposed in vitro to three strains of Pasteurella multocida, Immun., 39, 779, 1983.Google Scholar
  30. 30.
    Schaffner, A., Douglas, H., Braude, A>I>, and Davis, CE., Killing of Aspergillus spores depends on the abatomical source of the macrophage, Infect. Immun. 42, 1109, 1983.PubMedGoogle Scholar
  31. 31.
    Black, C.M., Beaman, B.L., Donovan, R.M., and Goldstein, E., Intracellular acid phosphatase content and ability of different macrophage populations to kill Nocardia asteroides, Infect. Immun., 47, 375, 1985.PubMedGoogle Scholar
  32. 32.
    Cleveland, R.P., Meltzer, M.S. and Zbar, B., Tumor cytotoxicity in vitro by macrophagtes from mice infected with Mycobacterium bovis strain BCG, J. Natl. Cancer Inst, 52, 1887, 1974.PubMedGoogle Scholar
  33. 33.
    Droller, MJ. and Remington, J.S., A role for the macrophage in the in vivo and invitro resistance to murine bladder tumor cell growth, Cancer Res., 35, 49, 1975.PubMedGoogle Scholar
  34. 34.
    Kaplan, A.M., Morahan, P.S., and Regilson, W., Induction of macrophage mediated tumor cell cytotoxicity by by pyran copolymer, J. Natl. Cancer Inst, 52, 1919, 1974.PubMedGoogle Scholar
  35. 35.
    Scott, M.T., In vitro cortisone sensitivity of nonspecific antitumor activity of Corynebacterium parvum activated mouse peritoneal macrophages. J. Natl. Cancer Inst., 54, 789, 1975.PubMedGoogle Scholar
  36. 36.
    Sone, S. and Fidler, I.J., In situ activation of tumoricidal properties in rat alveolar macrophages and rejection of experimental lung metastases by intravenous injections of Nocardia rubra cell wall skeleton, Cancer Immunol. Immunother., 12, 203, 1982.CrossRefGoogle Scholar
  37. 37.
    Chihara, G., Maeda, Y>Y>, Hamuro, J., Sasaki, T., and Fukuoka, F., Inhibition of mouse sarcoma 180 by the polysaccharide from Lentinus erodes, Nature (London), 222, 687. 1969.CrossRefGoogle Scholar
  38. 38.
    Chirigos, M.A., Ed., Immune modulation and control of neoplasia by adjuvant therapy, Progress in Cancer Research and Therapy, Vol. 7, Raven Press, New York, 1978.Google Scholar
  39. 39.
    Fenichel, R. and Chirigos, M.A., Eds., Immune Modulating Agents and Their Mechanisms, Vol. 25, Marcel Dekker, New york, 1985.Google Scholar
  40. 40.
    Halper, B., Corynebacterium parvum: Applications in Experimental and Clinical Onocology, Plenum Press, New Yor, 1975.Google Scholar
  41. 41.
    Hersh, E., Chirigos, M.A., and Mastrangelo, A., Eds., Augmenting agents in cancer therapy, Progress in Cancer Research and Therapy, Vol. 16, Raven Press, New York, 1981.Google Scholar
  42. 42.
    Mihich, E., Ed., Immunological Approaches to Cancer Therapeutics, John Wiley & Sons, New York, 1982.Google Scholar
  43. 43.
    Lederer, E., Synthetic immunostimulants derived from the bacterial cell wall, J. Med. Chem., 23, 819, 1980.PubMedCrossRefGoogle Scholar
  44. 44.
    Chedid, L. and Audibert, F., New approaches for control of infections using synthetic or semi-synthetic constructs containing MDP, Springer Semin. Immunopathol., 8, 401, 1985.PubMedCrossRefGoogle Scholar
  45. 45.
    Parant, M., Parant, F., Chedid, L., Yapo, A.,J.F., and Lederer, L., Fate of the synthetic immunoadjuvant muramyl depeptide (14 C-labelled) in the mouse, Int. J. Immunopharmacol., 1, 35, 1979.PubMedCrossRefGoogle Scholar
  46. 46.
    Chedid, L., Parant, M., Parant, F., Lefrancier, P., Choay, J., and Lederer, E., Enchancement of nonspecific immunity to Klebsiella pneumoniae infection by a synthetic immunoadjuvant (N-acetyl-muramyl-L-alanyl-D-isoglutamine) and several analogs, proc. Natl. Acad. Sci. U.S.A., 74, 2089, 1977.PubMedCrossRefGoogle Scholar
  47. 47.
    Dietrich, F.M., Sackmann, W., Zak, O., and Dukor, P., Synthetic muramyl dipeptide immunostimulants: protective effects and increased efficacy antibiotics in experimental bacterial and fungal infections in mice, in Current Chemotherapy and Infectious Disease, Vol. 2, Nelson, J.D. and Grassi, C., Ed., Am. Soc. Microbiol., Washington, D.C., 1980, 1730.Google Scholar
  48. 48.
    Fraser-Smith, E.B. and Matthews, T.R., Protective effects of muramyl dipeptide analogs against infections of Pseudomonas aeruginosa or Candida albicans in mice, Infect. Immunol., 34, 676, 1981.Google Scholar
  49. 49.
    Humphries, R.C., Heniki, P.R., Ferraresi, R.W., and Krahenbuhl, J.L., Effects of treatment with muramyl dipeptide and certain of its analogs on resistance to Listeria monocytogenes in mice, Infect. Immunol., 30, 462, 1980.Google Scholar
  50. 50.
    Matthers, T.R., and Fraser-Smith, E.B., Protective effect of muramyl dipeptide and analogs against Pseudomonas aeruginosa and Candida albicans infections in mice, Current Chemotherapy of Infectious Disease, Vol. 2, Am. Soc. Microbiol., Washington, D.C., 1980, 1734.Google Scholar
  51. 51.
    Onozuka, K., Saito-Taki, T., and Nakano, M., Effect of muramyl dipeptide analog on Salmonella enteritidis infection in beige mice with Chediak-Higashi syndrome, Microbiol. Immunol., 28, 1211, 1984.PubMedGoogle Scholar
  52. 52.
    Parant, M., Parant, F., and Chedid, L., Enhancement of the neonate’s nonspecific immunity to Klebsiella infection by muramyl dipeptide, a synthetic immunoadjuvant, Proc. Natl. Acad. Sci. U.S.A., 75, 3395, 1978.PubMedCrossRefGoogle Scholar
  53. 53.
    Kierszenbaum, F. and Ferraresi, R.W., Enhancement of host resistance against Trypanosoma cruzi infection by the immunoregulatory agent muramyl dipeptide, Infect. Immunol., 25, 273, 1979.Google Scholar
  54. 54.
    Krahenbuhl, J.L., and Humphries, R.C., Effects of treatment with muramyl dipeptide on resistance to Mycobacterium leprae and Mycobacterium marinum infection in mice, Immunopharmacology, 5, 329, 1983.PubMedCrossRefGoogle Scholar
  55. 55.
    Dietrich, F.M., Lukas, B., and Schmidt-Rupin, K.H., MTP-PE (synthetic muramyl peptide): prophylactic and therapeutic effects in experimental viral infections, Commun. 13th Int. Cong. Chemother., Vienna, August 28, 1983.Google Scholar
  56. 56.
    Koff, W.C., Fidler, I.J., Showalter, S.D., Chakrabarty, M.K., Hampar, B., Ceccorulli, L.M., and Kleinerman, E.S., Human monocytes activated by immunomodulators in liposomes lyse herpesvirus-infected but not normal cells, Science, 224, 1007, 1984.PubMedCrossRefGoogle Scholar
  57. 57.
    Poste, G., Kirsh, R., and Fidler, I.J., Cell surface receptors for lymphokines, Cell. Immunol. 44, 71, 1979.PubMedCrossRefGoogle Scholar
  58. 58.
    Andreesen, R., Bross, K.J., Osterholz, J., and Emmrich, F., Human macrophage maturation and heterogeneity: analysis with a newly generated set of monoclonal antibodies to differentiation antigens, Blood, 67_(5), 1257, 1986.Google Scholar
  59. 59.
    Shen, H.H., Talle, M.A., Goldstein, G., and Chess, L., Functional subsets of human monocytes defined by monoclonal antibodies. A distinct subset of monocytes contains the cells capable of inducing the autologous mixed lymphocytes culture, J., Immunol., 130, 698, 1983.Google Scholar
  60. 60.
    Zembala, M., Uracz, W., Ruggiero, I., Mytar, B., and Pryjma, J., Isolation and functional characterization of FcR+ and FcR− human monocyte subsets, J. Immunol., 133, 1293, 1984.PubMedGoogle Scholar
  61. 61.
    Schreiber, R.D., Pace, J.L., Russell, S.W., Altman, A., and Katz, D.H., Macrophageactivating factor produced by a T cell hybridoma: physiochemical and biosynthetic resemblance of γ-intergeron. J. Immunol., 131, 826, 1983.PubMedGoogle Scholar
  62. 62.
    Le, L., Prensky, W., Yip, Y.K., Chang, Z., Hoffman, T., Stevenson, H.C., Balazs, I., Sadlik, J.R., and Vilcek, J., Activation of human monocyte cytotoxicity by natural and recombinant immune interferon, J. Immunol., 131, 2821, 1984.Google Scholar
  63. 63.
    Schreiber, R.D., Pace, J.L., Russell, S.W., Altman, A., and Katz, D.H. Macrophage activating factor produced by a T cell hybridoma: physiochemical and biosynthetic resemblance to −-interferon, I. Immunol., 131, 826, 1083.Google Scholar
  64. 64.
    Roberts, W.K. and Vasil, A., Evidence for the identity of murine gamma interferon and macrophage activating factor, J. Interferon Res., 2, 519, 1982.PubMedCrossRefGoogle Scholar
  65. 65.
    Kleinerman, E.D., Zicht, R., Sarin, P.S., Gallo, R.C., and Fidler, J. Constitutive production and release of a lymphokine with macrophage activating factor activity distinct from γ-interferon by a human T cell leikemia virus-positive cell line, Cancer Res., rr, 4470, 1984.Google Scholar
  66. 66.
    Meltzer, M.S., Gilbreath, M., Nacy, C.A., and Schreiber, R.D., Macrophage activation factor from EL-A cells distinct from murine gamma interferon (IFN), Fed. Proc. Fed. Am. Soc. Biol., 44, (Abstr.), 1697, 1985.Google Scholar
  67. 67.
    Crawford, R., Hoover, D., Finbloom, D., Gilbrath, M., Nacy, C., and Meltzer, M., Physicochemical properties of a human lymphokine (LK) distinct from gamma interferon (IFN) that activates monocytes to kill Leishmania donovani, Fed. proc. Fed. Am. Soc. Exp. Bio., 44 (Abstr.) 1697, 1985.Google Scholar
  68. 68.
    Lee, J.C, Rebar, L., Young, P., Ruscetti, R.W., Hanna, N., and Poste, G., Identification and characterization of a human T cell line-derived lymphokine with MAF-like activity distinct from interferon-γ, J. Immunol, 136, 1322, 1986.PubMedGoogle Scholar
  69. 69.
    Lee, J.C, Badger, A.M., Johnson, W.J., Sung, C.P., and Horan, P., Human non-gamma interferon macrophage activating actor (MT-2/MAF) elicits multiple and cross-species effects on macrophage activationa, Abstr. Sixth Int. Congr. Immunol., 1986.Google Scholar
  70. 70.
    Onozaki, K., Matsushima, K., Kleinerman, E.D., Saito, T., and Oppenheim, J.J., Role of IL-1 in promoting human monocyte-mediated tumor cytotocivity, J. Ummunol., 135, 314, 1985.Google Scholar
  71. 71.
    Philip, R. and Epstein, L.B., TNF as immunomodulator and mediator of monocyte cytotoxicity induced by itself, IFN-γ and IL-1, Nature (London) 323, 86, 1986.CrossRefGoogle Scholar
  72. 72.
    Billiam, A., Damme, J.V., Opdenakker, G., Fibbe, W.E., Falkenburg, J.H.F., and Content, J., IL-1 as a cytokine inducer, Immunobiology, 172, 323, 1986.CrossRefGoogle Scholar
  73. 73.
    Malkovsky, M., Loveland, B., North, M., Asherton, G.L., Gao, L., Ward, P., and Fiers, W., Recombinant IL-2 directly augments the cytotocivity of human monocytes, Nature (London), 325, 262, 1987.CrossRefGoogle Scholar
  74. 74.
    Nathan, C.F>, Prendergast, T.J., Wiebe, M.E., Stanley, E.R., Platzer, E., Remold, H.B., Weite, K., Rubin, B.Y., and Murray, H.W., Activation of human macrophages. Comparison of their cytokines with interferon-γ, J. Exp. Med., 160, 600, 1984.PubMedCrossRefGoogle Scholar
  75. 75.
    Djeu, J.Y. and Blanchared, D.K., Gnereation of autoreactive killer cells against human monocytes/macrophages by IL-2, Lymphokine Res., 6 (Abstr.)., 1705, 1987.Google Scholar
  76. 76.
    Meltzer, M.S., Crawford, R.M., Finbloom, D.S., Phara, J., and Paul, W.E., BSF-1: a macrophage activation factor, Lymphokine Res., 6(Abstr.). 1719, 1987.Google Scholar
  77. 77.
    Esparza, I., Mannel, D., Ruppek, A., Falk, W., and Krammer, P.H., IFN-γ and lymphotoxin or TNF synergize to activate macrophages for tumoricidal and schistosomulicidal function, Lymphokine Res., 6(Abstr.), 1715, 1987.Google Scholar
  78. 78.
    Hoffman, M.K., The effects of TNF on the production of IL-1 by macrophages, Lymphokine Res., 5, 255, 1986.PubMedGoogle Scholar
  79. 79.
    Munker, R., Gasson, J., Ogawa, M., and Koeffer, H.P., Recombinant human TNF induces production of GM-CSF, Nature (London), 323, 79, 1986.CrossRefGoogle Scholar
  80. 80.
    Medcalf, D., The granulocyte-macrophage colony stimulating factors, Science, 229, 16, 1986.CrossRefGoogle Scholar
  81. 81.
    Weiser, W.Y., Van Niel, A., Clark, S.C., David, J.R., and Remold, H.G., Recombinant human GM-CSF activates intracellular killing of Leishmania donavani by human monocytes, Lymphokine Res., 6 (Abstr.), 1706, 1987.Google Scholar
  82. 82.
    Ralph, P., Warren, M.K., Nakoinz, I., Lee, M.T., Brindley, L., Sampson-Johannes, A., Kawaski, E.S., Ladner, M.B., Stickler, J.E., Boosman, A., Csejtey, J., and White, T.J., Biological properties and molecular biology of the human macriphage growth factor, CSF-1, Immunobiology, 172, 194, 1986.PubMedCrossRefGoogle Scholar
  83. 83.
    Warren, M.K. and Ralph, P., CSF-1 stimulates human monocyte production of interferon, TNF and colony stimulating activity, J. Immunol, 137, 2281, 1986.PubMedGoogle Scholar
  84. 84.
    Beller, D.I. and Ho, K., Regulation of macrophage population. V. Evaluation of the control of macrophage Ia expression in vitro, J. Immunol., 129, 971, 1982.PubMedGoogle Scholar
  85. 85.
    Nacy, C.A., James, S.L., Osier, C.N., and Meltzer, M.S., Activation of macrophages to kill Rickettsiae and Leishmania: disassociation of intracellular microbicidal activities and extracellular diestruction of neoplastic cells and helminths, Contemp. Top. Immunobiol., 14, 147, 1984.Google Scholar
  86. 86.
    Pace, J.L. and Russell, S.W., Activation of mouse macrophages for tumor cell killing. I. Quantitative analysis of interactions between lymphokine and LPS, J. Immunol., 126, 1863, 1981.PubMedGoogle Scholar
  87. 87.
    Bonvini, E., Hoffman, T., Herberman, R.B., and Varesio, L., Selective augmentation by recombinant interferon-γ of the intracellular content of S-adenosylmethionine in murine macrophages, J. Immunol., 136, 2596, 1986.PubMedGoogle Scholar
  88. 88.
    Varesio, L., Imbalanced accumulation of ribosomal RNA in macrophages activated in vivo or in vitro to a cytolytic stage, J. Immunol., 134, 1262, 1985.PubMedGoogle Scholar
  89. 89.
    Hamilton, T.A., Becton, D.B., Somers, S.D., Gray, P.W., and Adams, D.O., Interferon gamma modulates protein kinase C activity in murine peritoneal macrophages, J. Biol. Chem., 260, 1378, 1985.PubMedGoogle Scholar
  90. 90.
    Strassmann, G., Springer, T.A., Somers, S.D., and Adams, D.O., Mechanisms of tumor cell capture by activated macrophages: evidence for involvement of lymphocyte function-associated (LFA)-1 antigen, J. Immunol., 136, 4328, 1986.PubMedGoogle Scholar
  91. 91.
    MacKay, R.J. and Russell, S.W., Protein changes associated with stages of activation of mouse macrophages for tumor cell killing, J. Immunol., 137, 1391, 1986.Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • R. Kirsh
    • 1
  • P. J. Bugelski
    • 2
  1. 1.Departments of Drug DeliverySmithKline & French LaboratoriesKing of PrussiaUSA
  2. 2.Experimental PathologySmithKline & French LaboratoriesKing of PrussiaUSA

Personalised recommendations