Skip to main content
Top
Published in: Cancer Immunology, Immunotherapy 8/2010

01-08-2010 | Original Article

Characterizing the anti-tumor function of adoptively transferred NK cells in vivo

Authors: Hollie J. Pegram, Nicole M. Haynes, Mark J. Smyth, Michael H. Kershaw, Phillip K. Darcy

Published in: Cancer Immunology, Immunotherapy | Issue 8/2010

Login to get access

Abstract

Natural killer (NK) cells represent a promising cell type to utilize for effective adoptive immunotherapy. However, little is known about the important cytolytic molecules and signaling pathways used by NK cells in the adoptive transfer setting. To address this issue, we developed a novel mouse model to investigate the trafficking and mechanism of action of these cells. We demonstrate that methylcholanthrene-induced RKIK sarcoma cells were susceptible to NK cell-mediated lysis in vitro and in vivo following adoptive transfer of NK cells in C57BL/6 RAG-2−/−γc−/− mice. Cytotoxic molecules perforin, granzymes B and M as well as the death ligand TRAIL and pro-inflammatory cytokine IFN-γ were found to be important in the anti-tumor effect mediated by adoptively transferred NK cells. Importantly, we demonstrate that adoptively transferred NK cells could traffic to the tumor site and persisted in vivo which correlated with the anti-tumor effect observed. Overall, the results of this study have important implications for enhancing NK cell-based immunotherapies.
Literature
1.
go back to reference Yokoyama WM, Kim S, French AR (2004) The dynamic life of natural killer cells. Annu Rev Immunol 22:405–429CrossRefPubMed Yokoyama WM, Kim S, French AR (2004) The dynamic life of natural killer cells. Annu Rev Immunol 22:405–429CrossRefPubMed
3.
go back to reference Cavanaugh VJ, Raulet DH, Campbell AE (2007) Upregulation of CD94/NKG2A receptors and Qa-1b ligand during murine cytomegalovirus infection of salivary glands. J Gen Virol 88:1440–1445CrossRefPubMed Cavanaugh VJ, Raulet DH, Campbell AE (2007) Upregulation of CD94/NKG2A receptors and Qa-1b ligand during murine cytomegalovirus infection of salivary glands. J Gen Virol 88:1440–1445CrossRefPubMed
4.
go back to reference Gasser S, Orsulic S, Brown EJ, Raulet DH (2005) The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436:1186–1190CrossRefPubMed Gasser S, Orsulic S, Brown EJ, Raulet DH (2005) The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436:1186–1190CrossRefPubMed
5.
go back to reference Raulet DH, Guerra N (2009) Oncogenic stress sensed by the immune system: role of natural killer cell receptors. Nat Rev Immunol 9:568–580CrossRefPubMed Raulet DH, Guerra N (2009) Oncogenic stress sensed by the immune system: role of natural killer cell receptors. Nat Rev Immunol 9:568–580CrossRefPubMed
6.
go back to reference Smyth MJ, Thia KY, Cretney E et al (1999) Perforin is a major contributor to NK cell control of tumor metastasis. J Immunol 162:6658–6662PubMed Smyth MJ, Thia KY, Cretney E et al (1999) Perforin is a major contributor to NK cell control of tumor metastasis. J Immunol 162:6658–6662PubMed
7.
go back to reference Seki N, Hayakawa Y, Brooks AD et al (2003) Tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis is an important endogenous mechanism for resistance to liver metastases in murine renal cancer. Cancer Res 63:207–213PubMed Seki N, Hayakawa Y, Brooks AD et al (2003) Tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis is an important endogenous mechanism for resistance to liver metastases in murine renal cancer. Cancer Res 63:207–213PubMed
9.
go back to reference Smyth MJ, Crowe NY, Godfrey DI (2001) NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int Immunol 13:459–463CrossRefPubMed Smyth MJ, Crowe NY, Godfrey DI (2001) NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int Immunol 13:459–463CrossRefPubMed
10.
go back to reference Degli-Esposti MA, Smyth MJ (2005) Close encounters of different kinds: dendritic cells and NK cells take centre stage. Nat Rev Immunol 5:112–124CrossRefPubMed Degli-Esposti MA, Smyth MJ (2005) Close encounters of different kinds: dendritic cells and NK cells take centre stage. Nat Rev Immunol 5:112–124CrossRefPubMed
11.
go back to reference Smyth MJ, Cretney E, Kershaw MH, Hayakawa Y (2004) Cytokines in cancer immunity and immunotherapy. Immunol Rev 202:275–293CrossRefPubMed Smyth MJ, Cretney E, Kershaw MH, Hayakawa Y (2004) Cytokines in cancer immunity and immunotherapy. Immunol Rev 202:275–293CrossRefPubMed
12.
go back to reference Rosenberg S (1985) Lymphokine-activated killer cells: a new approach to immunotherapy of cancer. J Natl Cancer Inst 75:595–603PubMed Rosenberg S (1985) Lymphokine-activated killer cells: a new approach to immunotherapy of cancer. J Natl Cancer Inst 75:595–603PubMed
13.
go back to reference Bordignon C, Carlo-Stella C, Colombo MP et al (1999) Cell therapy: achievements and perspectives. Haematologica 84:1110–1149PubMed Bordignon C, Carlo-Stella C, Colombo MP et al (1999) Cell therapy: achievements and perspectives. Haematologica 84:1110–1149PubMed
14.
go back to reference Morecki S, Yacovlev E, Gelfand Y, Vilensky A, Slavin S (2004) Allogeneic versus syngeneic killer splenocytes as effector cells for the induction of graft-versus-tumor effect. Biol Blood Marrow Transplant 10:40–48CrossRefPubMed Morecki S, Yacovlev E, Gelfand Y, Vilensky A, Slavin S (2004) Allogeneic versus syngeneic killer splenocytes as effector cells for the induction of graft-versus-tumor effect. Biol Blood Marrow Transplant 10:40–48CrossRefPubMed
15.
go back to reference Kawase T, Matsuo K, Kashiwase K et al (2009) HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism. Blood 113:2851–2858CrossRefPubMed Kawase T, Matsuo K, Kashiwase K et al (2009) HLA mismatch combinations associated with decreased risk of relapse: implications for the molecular mechanism. Blood 113:2851–2858CrossRefPubMed
16.
go back to reference Ruggeri L, Capanni M, Urbani E et al (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295:2097–2100CrossRefPubMed Ruggeri L, Capanni M, Urbani E et al (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295:2097–2100CrossRefPubMed
17.
go back to reference Guven H, Gilljam M, Chambers BJ et al (2003) Expansion of natural killer (NK) and natural killer-like T (NKT)-cell populations derived from patients with B-chronic lymphocytic leukemia (B-CLL): a potential source for cellular immunotherapy. Leukemia 17:1973–1980CrossRefPubMed Guven H, Gilljam M, Chambers BJ et al (2003) Expansion of natural killer (NK) and natural killer-like T (NKT)-cell populations derived from patients with B-chronic lymphocytic leukemia (B-CLL): a potential source for cellular immunotherapy. Leukemia 17:1973–1980CrossRefPubMed
18.
go back to reference Alici E, Sutlu T, Bjorkstrand B et al (2008) Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components. Blood 111:3155–3162CrossRefPubMed Alici E, Sutlu T, Bjorkstrand B et al (2008) Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components. Blood 111:3155–3162CrossRefPubMed
19.
go back to reference Imai C, Iwamoto S, Campana D (2005) Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood 106:376–383CrossRefPubMed Imai C, Iwamoto S, Campana D (2005) Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood 106:376–383CrossRefPubMed
20.
go back to reference Cho D, Campana D (2009) Expansion and activation of natural killer cells for cancer immunotherapy. Korean J Lab Med 29:89–96CrossRefPubMed Cho D, Campana D (2009) Expansion and activation of natural killer cells for cancer immunotherapy. Korean J Lab Med 29:89–96CrossRefPubMed
21.
go back to reference Karre K, Ljunggren HG, Piontek G, Kiessling R (1986) Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319:675–678CrossRefPubMed Karre K, Ljunggren HG, Piontek G, Kiessling R (1986) Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319:675–678CrossRefPubMed
22.
go back to reference Pegram HJ, Jackson JT, Smyth MJ, Kershaw MH, Darcy PK (2008) Adoptive transfer of gene-modified primary NK cells can specifically inhibit tumor progression in vivo. J Immunol 181:3449–3455PubMed Pegram HJ, Jackson JT, Smyth MJ, Kershaw MH, Darcy PK (2008) Adoptive transfer of gene-modified primary NK cells can specifically inhibit tumor progression in vivo. J Immunol 181:3449–3455PubMed
23.
go back to reference Abdool K, Cretney E, Brooks AD et al (2006) NK cells use NKG2D to recognize a mouse renal cancer (Renca), yet require intercellular adhesion molecule-1 expression on the tumor cells for optimal perforin-dependent effector function. J Immunol 177:2575–2583PubMed Abdool K, Cretney E, Brooks AD et al (2006) NK cells use NKG2D to recognize a mouse renal cancer (Renca), yet require intercellular adhesion molecule-1 expression on the tumor cells for optimal perforin-dependent effector function. J Immunol 177:2575–2583PubMed
24.
go back to reference Takeda K, Smyth MJ, Cretney E et al (2002) Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development. J Exp Med 195:161–169CrossRefPubMed Takeda K, Smyth MJ, Cretney E et al (2002) Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development. J Exp Med 195:161–169CrossRefPubMed
25.
go back to reference Trapani JA, Smyth MJ (2002) Functional significance of the perforin/granzyme cell death pathway. Nat Rev Immunol 2:735–747CrossRefPubMed Trapani JA, Smyth MJ (2002) Functional significance of the perforin/granzyme cell death pathway. Nat Rev Immunol 2:735–747CrossRefPubMed
26.
go back to reference Screpanti V, Wallin RP, Ljunggren HG, Grandien A (2001) A central role for death receptor-mediated apoptosis in the rejection of tumors by NK cells. J Immunol 167:2068–2073PubMed Screpanti V, Wallin RP, Ljunggren HG, Grandien A (2001) A central role for death receptor-mediated apoptosis in the rejection of tumors by NK cells. J Immunol 167:2068–2073PubMed
27.
go back to reference Trapani JA (2001) Granzymes: a family of lymphocyte granule serine proteases. Genome Biol 2:3014 (reviews) Trapani JA (2001) Granzymes: a family of lymphocyte granule serine proteases. Genome Biol 2:3014 (reviews)
28.
go back to reference Cretney E, Takeda K, Yagita H, Glaccum M, Peschon JJ, Smyth MJ (2002) Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice. J Immunol 168:1356–1361PubMed Cretney E, Takeda K, Yagita H, Glaccum M, Peschon JJ, Smyth MJ (2002) Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice. J Immunol 168:1356–1361PubMed
29.
30.
go back to reference Rabinowich H, Vitolo D, Altarac S, Herberman RB, Whiteside TL (1992) Role of cytokines in the adoptive immunotherapy of an experimental model of human head and neck cancer by human IL-2-activated natural killer cells. J Immunol 149:340–349PubMed Rabinowich H, Vitolo D, Altarac S, Herberman RB, Whiteside TL (1992) Role of cytokines in the adoptive immunotherapy of an experimental model of human head and neck cancer by human IL-2-activated natural killer cells. J Immunol 149:340–349PubMed
31.
go back to reference Schroder K, Hertzog PJ, Ravasi T, Hume DA (2004) Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 75:163–189CrossRefPubMed Schroder K, Hertzog PJ, Ravasi T, Hume DA (2004) Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 75:163–189CrossRefPubMed
32.
go back to reference Smyth MJ, Swann J, Cretney E, Zerafa N, Yokoyama WM, Hayakawa Y (2005) NKG2D function protects the host from tumor initiation. J Exp Med 202:583–588CrossRefPubMed Smyth MJ, Swann J, Cretney E, Zerafa N, Yokoyama WM, Hayakawa Y (2005) NKG2D function protects the host from tumor initiation. J Exp Med 202:583–588CrossRefPubMed
33.
go back to reference Huang J, Khong HT, Dudley ME et al (2005) Survival, persistence, and progressive differentiation of adoptively transferred tumor-reactive T cells associated with tumor regression. J Immunother 28:258–267CrossRefPubMed Huang J, Khong HT, Dudley ME et al (2005) Survival, persistence, and progressive differentiation of adoptively transferred tumor-reactive T cells associated with tumor regression. J Immunother 28:258–267CrossRefPubMed
34.
go back to reference Zhou J, Dudley ME, Rosenberg SA, Robbins PF (2005) Persistence of multiple tumor-specific T-cell clones is associated with complete tumor regression in a melanoma patient receiving adoptive cell transfer therapy. J Immunother 28:53–62CrossRefPubMed Zhou J, Dudley ME, Rosenberg SA, Robbins PF (2005) Persistence of multiple tumor-specific T-cell clones is associated with complete tumor regression in a melanoma patient receiving adoptive cell transfer therapy. J Immunother 28:53–62CrossRefPubMed
35.
go back to reference Dudley ME, Wunderlich JR, Robbins PF et al (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298:850–854CrossRefPubMed Dudley ME, Wunderlich JR, Robbins PF et al (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298:850–854CrossRefPubMed
36.
go back to reference Besser MJ, Shapira-Frommer R, Treves AJ et al (2009) Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients. J Immunother 32:415–423CrossRefPubMed Besser MJ, Shapira-Frommer R, Treves AJ et al (2009) Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients. J Immunother 32:415–423CrossRefPubMed
37.
go back to reference Lakshmikanth T, Burke S, Ali TH et al (2009) NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo. J Clin Invest 119:1251–1263CrossRefPubMed Lakshmikanth T, Burke S, Ali TH et al (2009) NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo. J Clin Invest 119:1251–1263CrossRefPubMed
38.
go back to reference van den Broek MF, Kagi D, Zinkernagel RM, Hengartner H (1995) Perforin dependence of natural killer cell-mediated tumor control in vivo. Eur J Immunol 25:3514–3516CrossRefPubMed van den Broek MF, Kagi D, Zinkernagel RM, Hengartner H (1995) Perforin dependence of natural killer cell-mediated tumor control in vivo. Eur J Immunol 25:3514–3516CrossRefPubMed
39.
go back to reference Street SE, Cretney E, Smyth MJ (2001) Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97:192–197CrossRefPubMed Street SE, Cretney E, Smyth MJ (2001) Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97:192–197CrossRefPubMed
40.
go back to reference Bolitho P, Voskoboinik I, Trapani JA, Smyth MJ (2007) Apoptosis induced by the lymphocyte effector molecule perforin. Curr Opin Immunol 19:339–347CrossRefPubMed Bolitho P, Voskoboinik I, Trapani JA, Smyth MJ (2007) Apoptosis induced by the lymphocyte effector molecule perforin. Curr Opin Immunol 19:339–347CrossRefPubMed
41.
go back to reference Keefe D, Shi L, Feske S et al (2005) Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis. Immunity 23:249–262CrossRefPubMed Keefe D, Shi L, Feske S et al (2005) Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis. Immunity 23:249–262CrossRefPubMed
42.
go back to reference Metkar SS, Wang B, Aguilar-Santelises M et al (2002) Cytotoxic cell granule-mediated apoptosis: perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation. Immunity 16:417–428CrossRefPubMed Metkar SS, Wang B, Aguilar-Santelises M et al (2002) Cytotoxic cell granule-mediated apoptosis: perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation. Immunity 16:417–428CrossRefPubMed
43.
go back to reference Sarin A, Williams MS, Alexander-Miller MA, Berzofsky JA, Zacharchuk CM, Henkart PA (1997) Target cell lysis by CTL granule exocytosis is independent of ICE/Ced-3 family proteases. Immunity 6:209–215CrossRefPubMed Sarin A, Williams MS, Alexander-Miller MA, Berzofsky JA, Zacharchuk CM, Henkart PA (1997) Target cell lysis by CTL granule exocytosis is independent of ICE/Ced-3 family proteases. Immunity 6:209–215CrossRefPubMed
44.
go back to reference Darmon AJ, Nicholson DW, Bleackley RC (1995) Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B. Nature 377:446–448CrossRefPubMed Darmon AJ, Nicholson DW, Bleackley RC (1995) Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B. Nature 377:446–448CrossRefPubMed
45.
go back to reference Waterhouse NJ, Sedelies KA, Trapani JA (2006) Role of Bid-induced mitochondrial outer membrane permeabilization in granzyme B-induced apoptosis. Immunol Cell Biol 84:72–78CrossRefPubMed Waterhouse NJ, Sedelies KA, Trapani JA (2006) Role of Bid-induced mitochondrial outer membrane permeabilization in granzyme B-induced apoptosis. Immunol Cell Biol 84:72–78CrossRefPubMed
46.
go back to reference Kelly JM, Waterhouse NJ, Cretney E et al (2004) Granzyme M mediates a novel form of perforin-dependent cell death. J Biol Chem 279:22236–22242CrossRefPubMed Kelly JM, Waterhouse NJ, Cretney E et al (2004) Granzyme M mediates a novel form of perforin-dependent cell death. J Biol Chem 279:22236–22242CrossRefPubMed
47.
go back to reference Beresford PJ, Xia Z, Greenberg AH, Lieberman J (1999) Granzyme A loading induces rapid cytolysis and a novel form of DNA damage independently of caspase activation. Immunity 10:585–594CrossRefPubMed Beresford PJ, Xia Z, Greenberg AH, Lieberman J (1999) Granzyme A loading induces rapid cytolysis and a novel form of DNA damage independently of caspase activation. Immunity 10:585–594CrossRefPubMed
48.
go back to reference Ebnet K, Hausmann M, Lehmann-Grube F et al (1995) Granzyme A-deficient mice retain potent cell-mediated cytotoxicity. EMBO J 14:4230–4239PubMed Ebnet K, Hausmann M, Lehmann-Grube F et al (1995) Granzyme A-deficient mice retain potent cell-mediated cytotoxicity. EMBO J 14:4230–4239PubMed
49.
go back to reference Trapani JA, Bird PI (2008) A renaissance in understanding the multiple and diverse functions of granzymes? Immunity 29:665–667CrossRefPubMed Trapani JA, Bird PI (2008) A renaissance in understanding the multiple and diverse functions of granzymes? Immunity 29:665–667CrossRefPubMed
50.
go back to reference Buzza MS, Zamurs L, Sun J et al (2005) Extracellular matrix remodeling by human granzyme B via cleavage of vitronectin, fibronectin, and laminin. J Biol Chem 280:23549–23558CrossRefPubMed Buzza MS, Zamurs L, Sun J et al (2005) Extracellular matrix remodeling by human granzyme B via cleavage of vitronectin, fibronectin, and laminin. J Biol Chem 280:23549–23558CrossRefPubMed
51.
go back to reference Metkar SS, Menaa C, Pardo J et al (2008) Human and mouse granzyme A induce a proinflammatory cytokine response. Immunity 29:720–733CrossRefPubMed Metkar SS, Menaa C, Pardo J et al (2008) Human and mouse granzyme A induce a proinflammatory cytokine response. Immunity 29:720–733CrossRefPubMed
52.
go back to reference Robbins PF, Dudley ME, Wunderlich J et al (2004) Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy. J Immunol 173:7125–7130PubMed Robbins PF, Dudley ME, Wunderlich J et al (2004) Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy. J Immunol 173:7125–7130PubMed
53.
go back to reference Cooper MA, Bush JE, Fehniger TA et al (2002) In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells. Blood 100:3633–3638CrossRefPubMed Cooper MA, Bush JE, Fehniger TA et al (2002) In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells. Blood 100:3633–3638CrossRefPubMed
54.
go back to reference Prlic M, Blazar BR, Farrar MA, Jameson SC (2003) In vivo survival and homeostatic proliferation of natural killer cells. J Exp Med 197:967–976CrossRefPubMed Prlic M, Blazar BR, Farrar MA, Jameson SC (2003) In vivo survival and homeostatic proliferation of natural killer cells. J Exp Med 197:967–976CrossRefPubMed
55.
go back to reference Becknell B, Caligiuri MA (2005) Interleukin-2, interleukin-15, and their roles in human natural killer cells. Adv Immunol 86:209–239CrossRefPubMed Becknell B, Caligiuri MA (2005) Interleukin-2, interleukin-15, and their roles in human natural killer cells. Adv Immunol 86:209–239CrossRefPubMed
56.
go back to reference Hayakawa Y, Smyth MJ (2006) CD27 dissects mature NK cells into two subsets with distinct responsiveness and migratory capacity. J Immunol 176:1517–1524PubMed Hayakawa Y, Smyth MJ (2006) CD27 dissects mature NK cells into two subsets with distinct responsiveness and migratory capacity. J Immunol 176:1517–1524PubMed
57.
go back to reference Cooper MA, Fehniger TA, Caligiuri MA (2001) The biology of human natural killer-cell subsets. Trends Immunol 22:633–640CrossRefPubMed Cooper MA, Fehniger TA, Caligiuri MA (2001) The biology of human natural killer-cell subsets. Trends Immunol 22:633–640CrossRefPubMed
58.
go back to reference Colucci F, Caligiuri MA, Di Santo JP (2003) What does it take to make a natural killer? Nat Rev Immunol 3:413–425CrossRefPubMed Colucci F, Caligiuri MA, Di Santo JP (2003) What does it take to make a natural killer? Nat Rev Immunol 3:413–425CrossRefPubMed
59.
go back to reference Klingemann HG, Martinson J (2004) Ex vivo expansion of natural killer cells for clinical applications. Cytotherapy 6:15–22CrossRefPubMed Klingemann HG, Martinson J (2004) Ex vivo expansion of natural killer cells for clinical applications. Cytotherapy 6:15–22CrossRefPubMed
60.
go back to reference Fujisaki H, Kakuda H, Shimasaki N et al (2009) Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res 69:4010–4017CrossRefPubMed Fujisaki H, Kakuda H, Shimasaki N et al (2009) Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res 69:4010–4017CrossRefPubMed
61.
go back to reference Lundqvist A, Yokoyama H, Smith A, Berg M, Childs R (2009) Bortezomib treatment and regulatory T-cell depletion enhance the antitumor effects of adoptively infused NK cells. Blood 113:6120–6127CrossRefPubMed Lundqvist A, Yokoyama H, Smith A, Berg M, Childs R (2009) Bortezomib treatment and regulatory T-cell depletion enhance the antitumor effects of adoptively infused NK cells. Blood 113:6120–6127CrossRefPubMed
62.
go back to reference Roda JM, Parihar R, Carson WE 3rd (2005) CpG-containing oligodeoxynucleotides act through TLR9 to enhance the NK cell cytokine response to antibody-coated tumor cells. J Immunol 175:1619–1627PubMed Roda JM, Parihar R, Carson WE 3rd (2005) CpG-containing oligodeoxynucleotides act through TLR9 to enhance the NK cell cytokine response to antibody-coated tumor cells. J Immunol 175:1619–1627PubMed
63.
go back to reference Muller T, Uherek C, Maki G et al (2008) Expression of a CD20-specific chimeric antigen receptor enhances cytotoxic activity of NK cells and overcomes NK-resistance of lymphoma and leukemia cells. Cancer Immunol Immunother 57:411–423CrossRefPubMed Muller T, Uherek C, Maki G et al (2008) Expression of a CD20-specific chimeric antigen receptor enhances cytotoxic activity of NK cells and overcomes NK-resistance of lymphoma and leukemia cells. Cancer Immunol Immunother 57:411–423CrossRefPubMed
Metadata
Title
Characterizing the anti-tumor function of adoptively transferred NK cells in vivo
Authors
Hollie J. Pegram
Nicole M. Haynes
Mark J. Smyth
Michael H. Kershaw
Phillip K. Darcy
Publication date
01-08-2010
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 8/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-010-0848-7

Other articles of this Issue 8/2010

Cancer Immunology, Immunotherapy 8/2010 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine