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Human T Cells Specifically Activated Against Autologous Malignant Melanoma

Human T Cells Specifically Activated Against Autologous Malignant Melanoma Abstract • Lymphocytes from ten patients with melanoma were specifically stimulated in vitro with autologous melanoma cells and expanded in interleukin 2. Significant lysis of autologous melanoma cells was demonstrated in T cells derived from six of these patients. The mean percent of lysis of autologous tumor cells at an effector-target ratio of 20:1 was 46% among these six patients. The T cells derived from two patients developed specificity in lysing autologous melanoma cells. In both cases, specificity was enhanced by the in vitro stimulation with autologous tumor cells. Restimulation with autologous melanoma cells was associated with increasing specificity over time. Whether derived from peripheral blood lymphocytes or from lymph node cells, T cells from one patient lysed fresh autologous melanoma cells more potently than K562, allogeneic melanoma cells, and nonmelanoma cells. On day 38, at an effector-target ratio of 10:1, cell lysis of K562, an osteosarcoma, a pancreatic cancer, and three allogeneic melanomas was 3%, 4%, 7%, 8%, 7%, and 2%, respectively, while lysis of autologous melanoma cells was 47%. Specificity was maintained beyond day 60. The T cells could be expanded over 50-fold within one month. (Arch Surg 1987;122:1407-1411) References 1. Silverberg E, Lubera J: A review of American Cancer Society estimates of cancer cases and deaths . CA 1983;33:2-8. 2. Fernández-Cruz E, Gilman SC, Feldman JD: Immunotherapy of chemically induced sarcoma in rats: Characterization of the effector T-cell subset and nature of suppression . J Immunol 1982;128:1112-1117. 3. Eberlein TJ, Rosenstein M, Rosenberg SA: Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin 2 . J Exp Med 1982;156:385-397.Crossref 4. Cheever MA, Greenberg PD, Fefer A, et al: Augmentation of the antitumor therapeutic efficacy of long-term cultured T lymphocytes by in vivo administration of purified interleukin 2 . J Exp Med 1982;155:968-980.Crossref 5. Rosenberg SA, Lotze MT, Muul LM, et al: Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin 2 to patients with metastatic cancer . N Engl J Med 1985;313:1485-1492.Crossref 6. Shu S, Chou T, Rosenberg SA: In vitro sensitization and expansion with viable tumor cells and interleukin 2 in the generation of specific therapeutic effector cells . J Immunol 1986;136:3891-3898. 7. Seigler HF, Cox E, Mutzner F, et al: Specific active immunotherapy for melanoma . Ann Surg 1979;190:366-372.Crossref 8. Rosenberg SA, Lotze MT, Muul LM, et al: A new approach to the therapy of cancer based on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin 2 . Surgery 1986;100:262-272. 9. Rosenberg SA, Lotze MT, Muul LM, et al: 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 1987;316:889-897.Crossref 10. Balsari A, Fossati G, Taramelli D, et al: Allostimulation of patients' lymphocytes generates both T and NK-like cells cytotoxic for autologous melanoma . Br J Cancer 1985;52:73-80.Crossref 11. Kimura H, Yamaguchi Y, Fujisawa T: Cytotoxicity of autologous and allogeneic lymphocytes against cultured human lung cancer cells: Optimal conditions for the production of cytotoxic lymphocytes . Gan No Rinsho 1984;75:1006-1016. 12. Hersey P, Bindon C, Edwards A, et al: Induction of cytotoxic activity in human lymphocytes against autologous and allogeneic melanoma cells in vitro by culture with interleukin 2 . Int J Cancer 1981;28:695-703.Crossref 13. Hersey P, MacDonald M, Schibeci S, et al: Clonal analysis of cytotoxic T lymphocytes against autologous melanoma . Cancer Immunol Immunother 1986;22:15-23. 14. Anichini A, Fossati G, Parmiani G: Clonal analysis of cytotoxic T lymphocyte response to autologous human malignant melanoma . Int J Cancer 1985;35:683-689.Crossref 15. Muul LM, Spiess PJ, Director EP, et al: Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma . J Immunol 1987;138:989-995. 16. Akiyama M, Bean M, Sadamoto K, et al: Suppression of the responsiveness of lymphocytes from cancer patients triggered by co-culture with autologous tumor-derived cells . J Immunol 1984;131:510-519. 17. Mukherji B, Wilhelm S, Guha A, et al: Regulation of cellular immune response against autologous human melanoma: II. Mechanism of induction and specificity of suppression . J Immunol 1986;136:1893-1898. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Human T Cells Specifically Activated Against Autologous Malignant Melanoma

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Publisher
American Medical Association
Copyright
Copyright © 1987 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1987.01400240053009
Publisher site
See Article on Publisher Site

Abstract

Abstract • Lymphocytes from ten patients with melanoma were specifically stimulated in vitro with autologous melanoma cells and expanded in interleukin 2. Significant lysis of autologous melanoma cells was demonstrated in T cells derived from six of these patients. The mean percent of lysis of autologous tumor cells at an effector-target ratio of 20:1 was 46% among these six patients. The T cells derived from two patients developed specificity in lysing autologous melanoma cells. In both cases, specificity was enhanced by the in vitro stimulation with autologous tumor cells. Restimulation with autologous melanoma cells was associated with increasing specificity over time. Whether derived from peripheral blood lymphocytes or from lymph node cells, T cells from one patient lysed fresh autologous melanoma cells more potently than K562, allogeneic melanoma cells, and nonmelanoma cells. On day 38, at an effector-target ratio of 10:1, cell lysis of K562, an osteosarcoma, a pancreatic cancer, and three allogeneic melanomas was 3%, 4%, 7%, 8%, 7%, and 2%, respectively, while lysis of autologous melanoma cells was 47%. Specificity was maintained beyond day 60. The T cells could be expanded over 50-fold within one month. (Arch Surg 1987;122:1407-1411) References 1. Silverberg E, Lubera J: A review of American Cancer Society estimates of cancer cases and deaths . CA 1983;33:2-8. 2. Fernández-Cruz E, Gilman SC, Feldman JD: Immunotherapy of chemically induced sarcoma in rats: Characterization of the effector T-cell subset and nature of suppression . J Immunol 1982;128:1112-1117. 3. Eberlein TJ, Rosenstein M, Rosenberg SA: Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin 2 . J Exp Med 1982;156:385-397.Crossref 4. Cheever MA, Greenberg PD, Fefer A, et al: Augmentation of the antitumor therapeutic efficacy of long-term cultured T lymphocytes by in vivo administration of purified interleukin 2 . J Exp Med 1982;155:968-980.Crossref 5. Rosenberg SA, Lotze MT, Muul LM, et al: Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin 2 to patients with metastatic cancer . N Engl J Med 1985;313:1485-1492.Crossref 6. Shu S, Chou T, Rosenberg SA: In vitro sensitization and expansion with viable tumor cells and interleukin 2 in the generation of specific therapeutic effector cells . J Immunol 1986;136:3891-3898. 7. Seigler HF, Cox E, Mutzner F, et al: Specific active immunotherapy for melanoma . Ann Surg 1979;190:366-372.Crossref 8. Rosenberg SA, Lotze MT, Muul LM, et al: A new approach to the therapy of cancer based on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin 2 . Surgery 1986;100:262-272. 9. Rosenberg SA, Lotze MT, Muul LM, et al: 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 1987;316:889-897.Crossref 10. Balsari A, Fossati G, Taramelli D, et al: Allostimulation of patients' lymphocytes generates both T and NK-like cells cytotoxic for autologous melanoma . Br J Cancer 1985;52:73-80.Crossref 11. Kimura H, Yamaguchi Y, Fujisawa T: Cytotoxicity of autologous and allogeneic lymphocytes against cultured human lung cancer cells: Optimal conditions for the production of cytotoxic lymphocytes . Gan No Rinsho 1984;75:1006-1016. 12. Hersey P, Bindon C, Edwards A, et al: Induction of cytotoxic activity in human lymphocytes against autologous and allogeneic melanoma cells in vitro by culture with interleukin 2 . Int J Cancer 1981;28:695-703.Crossref 13. Hersey P, MacDonald M, Schibeci S, et al: Clonal analysis of cytotoxic T lymphocytes against autologous melanoma . Cancer Immunol Immunother 1986;22:15-23. 14. Anichini A, Fossati G, Parmiani G: Clonal analysis of cytotoxic T lymphocyte response to autologous human malignant melanoma . Int J Cancer 1985;35:683-689.Crossref 15. Muul LM, Spiess PJ, Director EP, et al: Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma . J Immunol 1987;138:989-995. 16. Akiyama M, Bean M, Sadamoto K, et al: Suppression of the responsiveness of lymphocytes from cancer patients triggered by co-culture with autologous tumor-derived cells . J Immunol 1984;131:510-519. 17. Mukherji B, Wilhelm S, Guha A, et al: Regulation of cellular immune response against autologous human melanoma: II. Mechanism of induction and specificity of suppression . J Immunol 1986;136:1893-1898.

Journal

Archives of SurgeryAmerican Medical Association

Published: Dec 1, 1987

References