Skip to main content
SpringerLink
Log in

Cancer, cytokines, and cytotoxic cells: Interleukin-2 in the immunotherapy of human neoplasms

  • Review
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Summary

Modern immunotherapy of human cancer has evolved as a rapidly expanding field of clinical and experimental research. Employing the systemic application of recombinant interleukin-2 (IL-2) in humans, Rosenberg and colleagues from the National Cancer Institute reported the regression of advanced metastatic tumors in approximately 10%–30% of patients treated. The additional adoptive transfer of autologous patient-derived activated lymphocytes was performed to enhance therapeutic efficacy. While the exact mechanisms of IL-2 based immunotherapy in cancer remain unclear, it has been hypothesized that both the IL-2 activated lymphocyte and its secretory products such as interferon-γ or tumor-necrosis factorβ may contribute to the lysis of tumor cells in vivo. Accordingly, research has been directed toward enhancing both the activation state and the specificity of IL-2 induced killer cells in humans. Based on in vitro and animal data, the retransfusion of tumor-infiltrating lymphocytes has been shown to mediate the regression of metastatic neoplasms in up to 50% of patients receiving systemic IL-2. Considerable toxicity from the use of high-dose IL-2 has prompted attempts to develop low-dose regimens which allow for the outpatient treatment of patients presenting poor prognosis. While in most clinical trials involving IL-2, patient follow-up has been short, and no or only limited data have become available from controlled prospective and randomized clinical studies, IL-2 has shown some promise in patients with metastatic renal cell cancer or malignant melanoma. Novel approaches toward the improvement of clinical efficacy of IL-2 include local (e.g., intracavitary) application or combinations with other cytokines such as interferon-α or cytostatic drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

LAK:

lymphokine-activated killer

IL-2:

interleukin-2

NK:

natural killer

MHC:

major histocompatibility complex

TCR:

T-cell receptor

CTL:

cytotoxic T lymphocyte

TIL:

tumor-infiltrating lymphocyte

ALAK:

adherent lymphokine-activated, killer

IFN-α :

interferon alpha

TNF-α :

tumor necrosis factor alpha

DTIC:

dacarbazine

References

  1. Aggarwal BB, Moffat B, Harkins RN (1984) Human lymphotoxin production by a lymphoblastoid cell line; purification and initial characterization. J Biol Chem 259:686–691

    Google Scholar 

  2. Allison MAK, Jones SE, McGuffey P (1989) Phase II trial of outpatient interleukin-2 in malignant lymphoma, chronic lymphocytic leukemia, and selected solid tumors. J Clin Oncol 7:75–80

    Google Scholar 

  3. Atzpodien J (1988) Immunotherapy: basic research and clinical outlook. J Cancer Res Clin Oncol 114:653–654

    Google Scholar 

  4. Atzpodien J, Wisniewski D, Gulati SC, Weite K, Knowles RW, Clarkson BD (1987) Interleukin-2- and mitogen-activated NK-like killer cells from highly purified human peripheral blood T cell (CD3+ N901−) cultures. Nat Immun Cell Growth Regul 6:129–140

    Google Scholar 

  5. Atzpodien J, Gulati SC, Kwon JH, Kushner BH, Shimazaki C, Bührer C, Öz S, Kolitz JE, Weite K, Clarkson BD (1988) Anti-tumor efficacy of interleukin-2-activated killer cells in human neuroblastoma ex vivo. Exp Cell Biol 56:236–244

    Google Scholar 

  6. Atzpodien J, Kirchner H, Hadam M, Bührer C, Dalimann I, Volgmann TH, Link H, Weite K, Poliwoda H (1988) Lymphokine-activated killing (LAK) and IL-2-receptor expression: perspective for an enhanced therapeutic efficacy. Blut:4 [Suppl] 221

    Google Scholar 

  7. Atzpodien J, Shimazaki C, Wisniewski D, Gulati S, Bührer C, Öz S, Link W, Poliwoda H, Weite K, Clarkson B (1989) Interleukin-2 and interferon-α in der adoptiven Immuntherapie des Plasmozytoms: Ein experimentelles Modell. In: Lutz D, Heinz R, Nowotny H, Stacher A (eds) Leukämien und Lymphome. Fortschritte und Hoffnungen. Urban and Schwarzenberg, München Wien Baltimore, p 211–212

    Google Scholar 

  8. Atzpodien J, Bührer C, Gulati SC, Wisniewski D, Öz S, Kirchner H, Benter T, Poliwoda H, Weite K, Clarkson B (1989) Induction of nonspecific cell-mediated cytotoxicity: a multisignal event and its cellular regulation. In: Neth R, Gallo RC (eds) Modern trends in human leukemia VIII. Springer, Heidelberg Berlin New York, p 273–280

    Google Scholar 

  9. Atzpodien J, Körfer A, Evers P, Franks CR, Knüver-Hopf J, Dallmann I, Pohl U, De Riese W, Schmoll HJ, Benter T, Poliwoda H, Kirchner H (1989) Subcutaneous interleukin-2 and interferon-α in patients with metastatic renal cell cancer: a preliminary report. Annals of Oncology (in press)

  10. Atzpodien J, Link H, Kirchner H, Stahl M, Volgmann TH, Mohr H, Pohl U, Freund M, Schmoll HJ, Poliwoda H (1989) A new, modified protocol for the adoptive immunotherapy of advanced and/or metastatic neoplasms using lymphokine-activated killer (LAK cells plus natural interleukin-2 (IL-2). In: Jungi WF, Senn HJ (eds) Krebs and Alternativmedizin II. Springer, Heidelberg Berlin New York (in press)

    Google Scholar 

  11. Atzpodien J, Palmer P, Loriaux E, Hadam M, Schmoll HJ, Poliwoda H, Kirchner H (1989) Biological activities of lowdose interleukin-2 in patients with advanced malignancy. Progress in Immunology VII. Springer, Heidelberg Berlin New York (in press)

    Google Scholar 

  12. Barth NM, Galazka AR, Rudnick SA (1988) Lymphokines and cytokines. In: Oldham RK (ed) Principles of cancer biotherapy. Raven, New York, p 273–290

    Google Scholar 

  13. Belldegrun A, Muul LM, Rosenberg SA (1988) Interleukin-2 expanded tumor infiltrating lymphocytes in human renal cell cancer: isolation, characterization, and antitumor activity. Cancer Res 48:206–214

    Google Scholar 

  14. Berd D, Mastrangelo MJ (1987) Effect of low dose cyclophosphamide on the immune system of cancer patients: reduction of T-suppressor function without depletion of the CD8+ subset. Cancer Res 47:3317–3321

    Google Scholar 

  15. Boldt DH, Mills BJ, Gemlo BT, Holden H, Mier J, Paietta E, McMannis JD, Escobedo LV, Sniecinski I, Rayner AA, Hawkins MJ, Atkins MB, Ciobanu N, Ellis TM (1988) Laboratory correlates of adoptive immunotherapy with recombinant interleukin-2 and lymphokine-activated killer cells in humans. Cancer Res 48:4409–4416

    Google Scholar 

  16. Bonilla F, Alvarez-Mon M, Merino F, de la Hera A, Alés JE, España P, Durántez A (1988) Interleukin-2 induces cytotoxic activity in lymphocytes from regional axillary nodes of breast cancer patients. Cancer 61:629–634

    Google Scholar 

  17. Brunda MJ, Bellantoni D, Sulich V (1987) In vivo antitumor activity of combinations of interferon alpha and interleukin-2 in a murine model. Correlation of efficacy with the induction of cells resembling natural killer cells. Int J Cancer 40:3948–3953

    Google Scholar 

  18. Carswell EA, Old LJ, Kassel RL (1975) An endotoxin induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 72:3666–3370

    Google Scholar 

  19. Cassel WA, Murray DR, Phillips HS (1983) A phase II study on the post-surgical management of stage II malignant melanoma with a Newcastle disease virus oncolysate. Cancer 52:856–860

    Google Scholar 

  20. Cohen PJ, Lotze MT, Roberts JR, Rosenberg SA, Jaffe ES (1987) The immunopathology of sequential tumor biopsies in patients treated with interleukin-2: correlation or response with T-cell infiltration and HLA-DR expression. Am J Pathol 129:208–216

    Google Scholar 

  21. Cortesina G, De Stefani A, Giovarelli M, Barioglio MG, Cavallo GV, Jemma C, Forni G (1988) Treatment of recurrent squamous cell carcinoma of the head and neck with low doses of interleukin-2 injected perilymphatically. Cancer 62:2482–2485

    Google Scholar 

  22. Darrow TL, Slingluff CL, Seigler HF (1988) Autologous lymph node cell-derived tumor-specific cytotoxic T-cells for use in adoptive immunotherapy of human melanoma. Cancer 62:85–91

    Google Scholar 

  23. Eberlein TJ, Schoof DD, Jung SE, Davidson D, Gramolini B, McGrath K, Massaro A, Wilson RE (1988) A new regimen of interleukin 2 and lymphokine-activated killer cells. Arch Intern Med 148:2571–2576

    Google Scholar 

  24. Farrar JJ, Benjamin WR, Hilfiker ML, Howard M, Farrar WL, Fuller-Farrar J (1982) The biochemistry, biology, and role of interleukin 2 in the induction of cytotoxic T-cell and antibody-forming B cell responses. Immunol Rev 63:129–166

    Google Scholar 

  25. Fisher B, Packard BS, Read EJ, Carrasquillo JA, Carter CS, Topalian SZ, Yang JC, Yolles P, Larson SM, Rosenberg SA (1989) Tumor localization of adoptively transferred indium-111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma. J Clin Oncol 7:250–261

    Google Scholar 

  26. Fisher RI, Coltman CA, Doroshow JH, Rayner AA, Hawkins MJ, Mier JW, Wiernik P, McMannis JD, Weiss GR, Margolin KA, Gemlo BT, Hoth DF, Parkinson DR, Paietta E (1988) Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 108:518–523

    Google Scholar 

  27. Flaherty L, Redman B, Chabot G, Martino S, Valdivieso M, Bradley E (1988) Combination of dacarbazine and interleukin-2 in metastatic malignant melanoma. Proc ASCO 7:254

    Google Scholar 

  28. Giacomini P, Aguzzi A, Pestha S (1984) Modulation by recombinant DNA leukocyte (α) and fibroblast (β) interferons of the expression and shedding of HLA- and tumorassiociated antigens. J Immunol 133:1649–1655

    Google Scholar 

  29. Gray PW, Aggarwal BB, Benton CV, Bringman TS, Henzel WJ, Jarrett JA, Leung DW, Moffat B, Ng P, Svedersky LP, Palladino MA, Nedwin GE (1984) Cloning and expression f cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity. Nature 312:721–724

    Google Scholar 

  30. Grossman Z, Herberman RB (1986) Natural killer cells and their relationship to T cells: hypothesis on the role of T cell receptor gene rearrangement on the course of adaptive differentiation. Cancer Res 46:2651–2658

    Google Scholar 

  31. Hameed A, Olsen KR, Lee MK, Lichtenheld MG, Podack ER (1989) Cytolysis by Ca-permeable transmembrane channels. Pore formation causes extensive DNA degradation and cell lysis. J Exp Med 169:765–777

    Google Scholar 

  32. Herberman RB, Hiserodt J, Vujanovic N, Balch C, Lotzová E, Bolhuis R, Golub S, Lanier LL, Phillips JH, Riccardi C, Ritz J, Santoni A, Schmidt RE, Uchida A (1987) Lymphokine-activated killer cell activity: characteristics of effector cells and their progenitors in blood and spleen. Immunol Today 8:178–181

    Google Scholar 

  33. Hérin M, Lemoine C, Weynants P, Vessière F, Van Pel A, Knuth A, Devos R, Boon T (1987) Production of stable cytolytic T-cell clones directed against autologous human melanoma. Int J Cancer 39:390–396

    Google Scholar 

  34. Hersey P, Bolhuis R (1987) ‘Nonspecific’ MHC-unrestricted killer cells and their receptors. Immunol Today 8:233–239

    Google Scholar 

  35. Klein E, Klein G, Nadkarni JS, Nadkarni JJ, Wigzell H, Clifford P (1968) Surface IgM-kappa specificity on a Burkitt lymphoma cell in vivo and in derived culture lines. Cancer Res 28:1300–1310

    Google Scholar 

  36. Kolitz JE, Wong GY, Weite K, Merluzzi VJ, Engert A, Bialas T, Polivka A, Bradley EC, Konrad M, Gnecco C, Oettgen HF, Mertelsmann R (1988) Phase I trial of recombinant interleukin-2 and cyclophosphamide: augmentation of cellular immunity and T-cell mitogenic response with long-term administration of rIL-2. J Biol Response Mod 7:457–472

    Google Scholar 

  37. Lee RE, Lotze MT, Skibber JM, Tucker E, Bonow RO, Ognibene FP, Carrasquillo JA, Shelhamer JH, Parrillo JE, Rosenberg SA (1989) Cardiorespiratory effects of immunotherapy with interleukin-2. J Clin Oncol 7:7–20

    Google Scholar 

  38. Lichtenheld MG, Olsen KJ, Lu P, Lowrey DM, Hameed A, Hengartner H, Podack ER (1988) Human perforin: structure and function. Nature 335:448–451

    Google Scholar 

  39. Lobo PI, Spencer CE (1989) Use of anti-HLA antibodies to mask major histocompatibility complex gene products on tumor cells can enhance susceptibility of these cells to lysis by natural killer cells. J Clin Invest 83:278–287

    Google Scholar 

  40. Lotze MT, Grimm EA, Mazumder A, Strausser JL, Rosenberg SA (1981) Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res 41:4420–4425

    Google Scholar 

  41. Lotzová E, Savary CA, Keating MJ (1982) Studies on the mechanism of defective natural killing in leukemia-diseased patients. Exp Hematol 10:83–88

    Google Scholar 

  42. Lozzio CV, Lozzio BB (1975) Human chronic myelogenous leukemia cell line with positive Philadelphia chromosome. Blood 45:321–334

    Google Scholar 

  43. McCune CS, O'Donnell RW, Marquis DM, Sahasrabudhe DM (1988) Renal carcinoma treated by vaccine-based specific immunotherapy: correlation of survival with skin testing by autologous tumor cells. Proc AACR 29:412

    Google Scholar 

  44. Melder RJ, Whiteside TL, Vujanovic NL, Hiserodt JC, Herberman RB (1988) A new approach to generating antitumor effectors for adoptive immunotherapy using human adherent lymphokine-activated killer cells. Cancer Res 48:3461–3469

    Google Scholar 

  45. Merchant RE, Grant AJ, Merchant LH, Young HF (1988) Adoptive immunotherapy for recurrent glioblastoma multiforme using lymphokine activated killer cells and recombinant interleukin-2. Cancer 62:665–671

    Google Scholar 

  46. Mergurian PA, Donahue L, Cockett AT (1987) Intraluminal interleukin-2 and bacillus Calmette-Guérin for treatment of bladder cancer: a preliminary report. J Urol 137:216–219

    Google Scholar 

  47. Mitchell MS, Kempf RA, Harel W, Shau H, Boswell WD, Lind S, Bradley EC (1988) Effectiveness and tolerability of low-dose cyclophosphamide and low-dose intravenous interleukin-2 disseminated melanoma. J Clin Oncol 6:409–424

    Google Scholar 

  48. Morris DG, Pross HF (1989) Studies of lymphokine-activated killer (LAK) cells. I. Evidence using novel monoclonal antibodies that most human LAK precursor cells share a common surface marker. J Exp Med 169:717–736

    Google Scholar 

  49. Nedwin GE, Svedfesky LP, Bringman R (1985) Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta. J Immunol 135:2492–2497

    Google Scholar 

  50. Nishihara K, Miyatake S, Sakata T, Yamashita J, Kikuchi H, Kawade Y, Zu Y, Namba Y, Hanaoka M, Watanabe Y (1988) Augmentation of tumor targeting in a line of glioma-specific mouse cytotoxic T-lymphocytes by retroviral expression of mouse τ-interferon complementary DNA. Cancer Res 48:4730–4735

    Google Scholar 

  51. Oldham RK (1988) Biotherapy: general principles. In: Oldham RK (ed) Principles of cancer biotherapy. Raven, New York, pp 1–20

    Google Scholar 

  52. Ortaldo JR, Longo DL (1988) Human natural lymphocyte effector cells: definition, analysis of activity, and clinical effectiveness. JNCI 80:999–1010

    Google Scholar 

  53. Ortaldo JR, Mason AT, Gerard JP, Henderson LE, Farrar W, Hopkins RF, Herberman RB, Rabin H (1984) Effects of natural and recombinant IL 2 on regulation of IFN production and natural killer activity: lack of involvement of the Tac antigen for these immunoregulatory effects. J Immunol 133:779–783

    Google Scholar 

  54. Podack ER, Konigsberg PJ (1984) Cytolytic T-cell granules: isolation, structural, biochemical and functional characterization. J Exp Med 160:695–710

    Google Scholar 

  55. Reynolds CW, Ortaldo JR (1987) Natural killer activity: the definition of a function rather than a cell type. Immunol Today 8:172–174

    Google Scholar 

  56. Rosenberg SA (1988) The development of new immunotherapies for the treatment of cancer using interleukin-2. Ann Surg 208:121–135

    Google Scholar 

  57. Rosenberg SA (1988) Immunotherapy of cancer using interleukin 2: Current status and future prospects. Immunol Today 9:58–62

    Google Scholar 

  58. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shilone E, Vetto JT, Seipp CA, Simpson C, Reichert CM (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313:1485–1492

    Google Scholar 

  59. Rosenberg SA, Spiess P, Lafreniere R (1986) A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233:1318–1321

    Google Scholar 

  60. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, White DE (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316:889–897

    Google Scholar 

  61. Rosenberg SA, Lotze MT, Mulé JJ (1988) New approaches to the immunotherapy of cancer using interleukin-2. Ann Intern Med 108:853–864

    Google Scholar 

  62. Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA, Simpson C, Carter C, Bock S, Schwartzentruber D, Wei JP, White DE (1988) Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. N Engl J Med 319:1676–1680

    Google Scholar 

  63. Rosenstein M, Ettinghausen SE, Rosenberg SA (1986) Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin-2. J Immunol 137:1735–1742

    Google Scholar 

  64. Royer HD, Reinherz EL (1987) T lymphocytes: ontogeny, function, and relevance to clinical disorders. N Engl J Med 317:1136–1142

    Google Scholar 

  65. Schirrmacher V (1987) Tumorzellimmunogenität und T-Zell-vermittelte Antitumorimmunreaktionen. Modulation und Einsatz in der Immuntherapie. Arzneimittel Forschung/Drug Res 37:259–262

    Google Scholar 

  66. Shimazaki C, Atzpodien J, Wisniewski D, Gulati SC, Kolitz JE, Clark-son BD (1988) Cell-mediated toxicity of interleukin-2-activated lymphocytes against autologous and allogeneic human myeloma cells. Acta Haematol (Basel) 80:203–209

    Google Scholar 

  67. Siegel JP, Sharon M, Smith PL, Leonard WJ (1987) The IL-2 receptorβ chain (p70): role in mediating signals for LAK, NK, and proliferative activities. Science 238:75–78

    Google Scholar 

  68. Spiegel RE (1987) The alpha interferons: clinical overview. Sem Oncol 14:1–12

    Google Scholar 

  69. Stewart J, Belinson J, Grant B, Dorighi J, Albertini R, Moore A, Branda R (1988) Phase I evaluation of intraperitoneal interleukin-2 and lymphokine activated killer cells in patients with ovarian cancer. Proceedings of ASCO 7:162

    Google Scholar 

  70. Stötter H, Wiebke EA, Tomita S, Belldegrun A, Topalian S, Rosenberg SA, Lotze MT (1989) Cytokines alter target cell susceptibility to lysis. J Immunol 142:1767–1773

    Google Scholar 

  71. Taniguchi T, Matsui H, Fujita T, Takaoka C, Kashima N, Yoshimoto R, Hamuro J (1983) Structure and expression of a cloned cDNA for human interleukin-2. Nature (London) 302:305–310

    Google Scholar 

  72. Topalian SL, Solomon D, Avis FP, Chang AE, Freersen DL, Linehan WM, Lotze MT, Robertson CN, Seipp CA, Simon P, Simpson CG, Rosenberg SA (1988) Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study. J Clin Oncol 6:839–853

    Google Scholar 

  73. Trinchieri G, Perussia B (1985) Immune interferon: a pleiotropic lymphokine with multiple effects. Immunol Today 6:131–136

    Google Scholar 

  74. Tsudo M, Goldman CK, Bongiovanni KF, Chan WC, Winton EF, Yagita M, Grimm EA, Waldmann TA (1987) The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells. Proc Natl Acad Sci USA 84:5394–5398

    Google Scholar 

  75. Uchida A, Moore M, Klein E (1988) Autologous mixed lymphocyte-tumor reaction and autologous mixed lymphocyte reaction. II. Generation of specific and non-specific killer T cells capable of lysing autologous tumor. Int J Cancer 41:651–656

    Google Scholar 

  76. Wang HM, Smith KA (1987) The interleukin 2 receptors. J Exp Med 166:1055–1069

    Google Scholar 

  77. Weite K, Wang CY, Mertelsmann R, Venuta S, Feldmann S, Moore MAS (1982) Purification of human interleukin 2 to apparent homogeneity and its molecular heterogeneity. J Exp Med 156:454–464

    Google Scholar 

  78. West WH, Tauer KW, Yannelli JR, Marshall GD, Orr DW, Thurman GB, Old-ham RK (1987) Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. N Engl J Med 316:898–905

    Google Scholar 

  79. Yamamura T, Fujitani Y, Kawauchi T, Wada E, Kobayashi Y, Yoshikawa K, Owaga H, Sugiyama H, Ohsawa M, Aozasa K (1989) Histological evidence of natural killer cell aggregation against malignant melanoma induced by adoptive immunotherapy with lymphokine-activated killer cells. J Pathol 157:201–204

    Google Scholar 

  80. Yoshida S, Tanaka R, Takai N, Ono K (1988) Local administration of autologous lymphokine-activated killer cells and recombinant interleukin 2 to patients with malignant brain tumors. Cancer Res 48:5011–5016

    Google Scholar 

  81. Young JDE, Liu CC (1988) Multiple mechanisms of lymphocyte-mediated killing. Immunol Today 9:140–144

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Abteilung für Hämatologie und Onkologie, Medizinische Hochschule Hannover, Deutschland

    J. Atzpodien & H. Kirchner

  2. Zentrum Innere Medizin und Dermatologie, Medizinische Hochschule Hannover, Deutschland

    J. Atzpodien & H. Kirchner

Authors
  1. J. Atzpodien
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Kirchner
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Atzpodien, J., Kirchner, H. Cancer, cytokines, and cytotoxic cells: Interleukin-2 in the immunotherapy of human neoplasms. Klin Wochenschr 68, 1–11 (1990). https://doi.org/10.1007/BF01648882

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01648882

Key words

Search

Navigation