- Email: [email protected]
Overview: NK-cell-based Immunotherapies: Toward & Into Clinical Trials
Clinical Immunology 177 (2017) 1–2
Contents lists available at ScienceDirect
Clinical Immunology journal homepage: www.elsevier.com/locate/yclim
Editorial
Overview: NK-cell-based Immunotherapies: Toward & Into Clinical Trials
According to PubMed (https://www.ncbi.nlm.nih.gov/pubmed/ NK%20cell), there are approximately 59,000 citations for "NK cell" (Fig. 1A), beginning in the first half of the 20th Century with variations on malignant histocytic reticulosis followed by reference to the evidently unrelated Nikolaĭ Konstantinovich Kol'tsov on the centennial of his birth in 1972 ! However, the “Natural Killer cells” we know and love really began to be understood in the 70s (Fig. 1A,B), alongside other lymphocyte subsets. Early experiments defined NK cells and established NK capability in ‘natural killing’ and antibody-dependent cell-mediated cytotoxicity assays using NK cells from mice and man. This included pioneering work of Hans Wigzell and colleagues as well as Laurie Glimcher and Harvey Cantor in mice [1–3], Puissant, Halldén and their colleagues in man, and Ronald Herberman et al. with both species and more [4–7]. Excellent current reviews written by some of the other key contributors since, further comprehensively describe the history and recent status of NK cell research [8–14]. There have been 2 waves of increases in publications on bona fide ‘Natural Killer cells (Fig. 1A), up to the end of the 1980s and after a ‘trough’ around 1990. So we could perhaps be considered currently in the renaissance of NK cells, in which molecular, in vivo and structural details as well as translational understanding have blossomed: NK cells are returning back from the bench to patients. Importantly the refined understanding of this important cytotoxic cell are allowing them to emerge as a promising therapeutic which is now seeing rapid advancement. This issue of Clin. Immunology brings together a series of reviews and papers by groups involved all aspects of ‘NK cell-ology’. These include the latest understanding on NK cells [21] and NK cells in vivo [23] as well as from groups involved in clinical trials related to NK cells [15, 20]. These trials have so far mostly relied on either specific matching of KIR haplotypes in thes context of transplantation or adoptive NK cell transfer since the beginning of the 21st century [8,10–12,15,20], no easy task, since NK cells do not rely only on IL-2 for their rapid expansion, unlike T cells. Trials with adoptive transfers to date have been mostly in various solid and especially hematological malignancies [8, 10–12,15,20], and there has been great innovation in the realm of adoptive transfer cell expansion [15]. Other NK-related approaches are underway and will likely lead to precise clinical applications [20]. Also included is a review covering the expanding understanding of the cell biology of NK [21]. Further reviews / papers cover NK cell involvement in spectrum of other diseases [16–19]. Finally there are reports of how to monitor and visualize murine and human NK cells [22,23]. More specifically, Lee et al. [15] discuss the direct treatment of cancer patients with NK-related therapies and how the contrasting approaches have yielded distinct outcomes. Viel et al. [16] describe NK cells in obese subjects and how NK cells might contribute to critical
http://dx.doi.org/10.1016/j.clim.2017.05.004 1521-6616/© 2017 Elsevier Inc. All rights reserved.
inflammation. Vely et al. [17] describe NK cells from patients with primary immune thrombocytopenia. In turn, Bryceson et al. [18] describe lessons learned from NK cells in patients with primary immunodeficiencies. Gardiner et al. [19] present their findings on the relation of NK cell populations to a specific autoimmune disease, psoriasis vulgaris. Guimaraes et al. [20] review progress on use of NK cells to treat metastatic cancer and future clinical trial approaches. Fehniger et al. [21] discuss NK cell development and function controlled by both transcriptional and post-transcriptional regulation. Mace et, al. describe quantitative measurement of NK cell function in human NK cells, established by these authors, using functional imaging cytometry [22]. Finally, Basse et al. [23] compare and contrast the roles of NK cells and T cell populations in model anti-cancer responses and how NK cells augment CD8 T cell anti-tumor immunity with elegant state-of-the-art in vivo imaging studies. With NK cells involved in bone marrow transplant for many years and in direct early clinical development for a decade now, it is to be hoped that their optimal and safe therapeutic use will be rapidly and efficiently defined. It appears that NK cell-based immunotherapies, in combination with other standard therapies, can be fully established for a range of malignant, infectious, and other diseases in the near future. These novel approaches build upon a rich history of innovation and experimental biology in NK cells, some of which is recounted in this volume along with perspectives on where it all might likely go. References [1] R. Kiessling, E. Klein, H. Wigzell, "Natural" killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype, Eur. J. Immunol. 5 (2) (Feb 1975) 112–117. [2] R. Kiessling, E. Klein, H. Pross, H. Wigzell, "Natural" killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell, Eur. J. Immunol. 5 (2) (Feb 1975) 117–121. [3] L. Glimcher, F.W. Shen, H. Cantor, Identification of a cell-surface antigen selectively expressed on the natural killer cell, J. Exp. Med. 145 (1) (Jan 1 1977) 1–9. [4] R.B. Herberman, S. Bartram, J.S. Haskill, M. Nunn, H.T. Holden, W.H. West, Fc receptors on mouse effector cells mediating natural cytotoxicity against tumor cells, J. Immunol. 119 (1) (Jul 1977) 322–326. [5] M. Boyiadzis, K.A. Foon, R.B. Herberman, NK cells in cancer immunotherapy: three decades of discovery, Discov. Med. 6 (36) (Dec 2006) 243–248. [6] J. Pavie-Fischer, F.M. Kourilsky, F. Picard, P. Banzet, A. Puissant, Cytotoxicity of lymphocytes from healthy subjects and from melanoma patients against cultured melanoma cells, Clin. Exp. Immunol. 21 (3) (Sep 1975) 430–441. [7] H. Perlmann, P. Perlmann, G.R. Pape, G. Halldén, Purification, fractionation and assay of antibody-dependent lymphocytic effector cells (K cells) in human blood, Scand. J. Immunol. (Suppl. 5) (Jun 1976) 57–68. [8] D.M. Benson Jr., M.A. Caligiuri, Killer immunoglobulin-like receptors and tumor immunity, Cancer Immunol. Res. 2 (2) (Feb 2014) 99–104. [9] P.H. Kruse, J. Matta, S. Ugolini, E. Vivier, Natural cytotoxicity receptors and their ligands, Immunol. Cell Biol. 92 (3) (Mar 2014) 221–229.
2
Editorial
A.
“ Natural Killer cells”
1975 1980 1985 1990 1995 2000 2005 2010 2015
B.
“NKcells”
[11] W. Leung, Infusions of allogeneic natural killer cells as cancer therapy, Clin. Cancer Res. 20 (13) (Jul 1 2014) 3390–3400. [12] L. Moretta, E. Montaldo, P. Vacca, G. Del Zotto, F. Moretta, P. Merli, F. Locatelli, M.C. Mingari, Human natural killer cells: origin, receptors, function, and clinical applications, Int. Arch. Allergy Immunol. 164 (4) (2014) 253–264. [13] T. Lysakova-Devine, C. O'Farrelly, Tissue-specific NK cell populations and their origin, J. Leukoc. Biol. 96 (6) (Dec 2014) 981–990. [14] M.G. Morvan, L.L. Lanier, NK cells and cancer: you can teach innate cells new tricks, Nat. Rev. Cancer 16 (1) (Jan 2016) 7–19. [15] Natural Killer Cell Adoptive Immunotherapy: Coming of Age. Dean Lee. [16] Alteration of NK cell phenotype and function in obese individuals. Sébastien Viel. [17] NK cell compartment in the peripheral blood and spleen in adult patients with primary immune thrombocytopenia. Frederic Vely. [18] Natural killer cell biology illuminated by primary immunodeficiency syndromes in humans. Yenan Bryceson. [19] Natural killer cells from psoriasis vulgaris patients have reduced levels of cytotoxicity associated degranulation and cytokine production. Clair M Gardiner. [20] Bench to bedside: NK cells and control of metastasis. Fernando Guimaraes [21] Transcriptional and post-transcriptional regulation of NK cell development and function. Todd Fehniger. [22] Quantification of Natural Killer Cell Polarization and Visualization of Synaptic Granule Externalization by Imaging Flow Cytometry. Emily Mace & Mark Smyth. [23] Adoptive Transfer of Natural Killer Cells Promotes the Anti-Tumor Efficacy of T Cells (MS & video). Per Basse.
Mark A. Exley E-mail address: [email protected] Jordan S. Orange
1975 1980 1985 1990 1995 2000 2005 2010 2015 Fig. 1. Citations in PubMed with ‘NK cells’ in Abstract, Title, &/or Keywords. A. Search used the terms “Natural Killer cells” recovered approximately 40,000 citations. B. Use of the exact phrase “NK cell(s)” produced about 1/2 as many (~20,000) citations with a more uniformly rising distribution.
[10] A.S. Chretien, A. Le Roy, N. Vey, T. Prebet, D. Blaise, C. Fauriat, D. Olive, CancerInduced Alterations of NK-Mediated Target Recognition: Current and Investigational Pharmacological Strategies Aiming at Restoring NK-Mediated Anti-Tumor Activity, Front. Immunol. 5 (Mar 24 2014) 122.
Contents lists available at ScienceDirect
Clinical Immunology journal homepage: www.elsevier.com/locate/yclim
Editorial
Overview: NK-cell-based Immunotherapies: Toward & Into Clinical Trials
According to PubMed (https://www.ncbi.nlm.nih.gov/pubmed/ NK%20cell), there are approximately 59,000 citations for "NK cell" (Fig. 1A), beginning in the first half of the 20th Century with variations on malignant histocytic reticulosis followed by reference to the evidently unrelated Nikolaĭ Konstantinovich Kol'tsov on the centennial of his birth in 1972 ! However, the “Natural Killer cells” we know and love really began to be understood in the 70s (Fig. 1A,B), alongside other lymphocyte subsets. Early experiments defined NK cells and established NK capability in ‘natural killing’ and antibody-dependent cell-mediated cytotoxicity assays using NK cells from mice and man. This included pioneering work of Hans Wigzell and colleagues as well as Laurie Glimcher and Harvey Cantor in mice [1–3], Puissant, Halldén and their colleagues in man, and Ronald Herberman et al. with both species and more [4–7]. Excellent current reviews written by some of the other key contributors since, further comprehensively describe the history and recent status of NK cell research [8–14]. There have been 2 waves of increases in publications on bona fide ‘Natural Killer cells (Fig. 1A), up to the end of the 1980s and after a ‘trough’ around 1990. So we could perhaps be considered currently in the renaissance of NK cells, in which molecular, in vivo and structural details as well as translational understanding have blossomed: NK cells are returning back from the bench to patients. Importantly the refined understanding of this important cytotoxic cell are allowing them to emerge as a promising therapeutic which is now seeing rapid advancement. This issue of Clin. Immunology brings together a series of reviews and papers by groups involved all aspects of ‘NK cell-ology’. These include the latest understanding on NK cells [21] and NK cells in vivo [23] as well as from groups involved in clinical trials related to NK cells [15, 20]. These trials have so far mostly relied on either specific matching of KIR haplotypes in thes context of transplantation or adoptive NK cell transfer since the beginning of the 21st century [8,10–12,15,20], no easy task, since NK cells do not rely only on IL-2 for their rapid expansion, unlike T cells. Trials with adoptive transfers to date have been mostly in various solid and especially hematological malignancies [8, 10–12,15,20], and there has been great innovation in the realm of adoptive transfer cell expansion [15]. Other NK-related approaches are underway and will likely lead to precise clinical applications [20]. Also included is a review covering the expanding understanding of the cell biology of NK [21]. Further reviews / papers cover NK cell involvement in spectrum of other diseases [16–19]. Finally there are reports of how to monitor and visualize murine and human NK cells [22,23]. More specifically, Lee et al. [15] discuss the direct treatment of cancer patients with NK-related therapies and how the contrasting approaches have yielded distinct outcomes. Viel et al. [16] describe NK cells in obese subjects and how NK cells might contribute to critical
http://dx.doi.org/10.1016/j.clim.2017.05.004 1521-6616/© 2017 Elsevier Inc. All rights reserved.
inflammation. Vely et al. [17] describe NK cells from patients with primary immune thrombocytopenia. In turn, Bryceson et al. [18] describe lessons learned from NK cells in patients with primary immunodeficiencies. Gardiner et al. [19] present their findings on the relation of NK cell populations to a specific autoimmune disease, psoriasis vulgaris. Guimaraes et al. [20] review progress on use of NK cells to treat metastatic cancer and future clinical trial approaches. Fehniger et al. [21] discuss NK cell development and function controlled by both transcriptional and post-transcriptional regulation. Mace et, al. describe quantitative measurement of NK cell function in human NK cells, established by these authors, using functional imaging cytometry [22]. Finally, Basse et al. [23] compare and contrast the roles of NK cells and T cell populations in model anti-cancer responses and how NK cells augment CD8 T cell anti-tumor immunity with elegant state-of-the-art in vivo imaging studies. With NK cells involved in bone marrow transplant for many years and in direct early clinical development for a decade now, it is to be hoped that their optimal and safe therapeutic use will be rapidly and efficiently defined. It appears that NK cell-based immunotherapies, in combination with other standard therapies, can be fully established for a range of malignant, infectious, and other diseases in the near future. These novel approaches build upon a rich history of innovation and experimental biology in NK cells, some of which is recounted in this volume along with perspectives on where it all might likely go. References [1] R. Kiessling, E. Klein, H. Wigzell, "Natural" killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype, Eur. J. Immunol. 5 (2) (Feb 1975) 112–117. [2] R. Kiessling, E. Klein, H. Pross, H. Wigzell, "Natural" killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell, Eur. J. Immunol. 5 (2) (Feb 1975) 117–121. [3] L. Glimcher, F.W. Shen, H. Cantor, Identification of a cell-surface antigen selectively expressed on the natural killer cell, J. Exp. Med. 145 (1) (Jan 1 1977) 1–9. [4] R.B. Herberman, S. Bartram, J.S. Haskill, M. Nunn, H.T. Holden, W.H. West, Fc receptors on mouse effector cells mediating natural cytotoxicity against tumor cells, J. Immunol. 119 (1) (Jul 1977) 322–326. [5] M. Boyiadzis, K.A. Foon, R.B. Herberman, NK cells in cancer immunotherapy: three decades of discovery, Discov. Med. 6 (36) (Dec 2006) 243–248. [6] J. Pavie-Fischer, F.M. Kourilsky, F. Picard, P. Banzet, A. Puissant, Cytotoxicity of lymphocytes from healthy subjects and from melanoma patients against cultured melanoma cells, Clin. Exp. Immunol. 21 (3) (Sep 1975) 430–441. [7] H. Perlmann, P. Perlmann, G.R. Pape, G. Halldén, Purification, fractionation and assay of antibody-dependent lymphocytic effector cells (K cells) in human blood, Scand. J. Immunol. (Suppl. 5) (Jun 1976) 57–68. [8] D.M. Benson Jr., M.A. Caligiuri, Killer immunoglobulin-like receptors and tumor immunity, Cancer Immunol. Res. 2 (2) (Feb 2014) 99–104. [9] P.H. Kruse, J. Matta, S. Ugolini, E. Vivier, Natural cytotoxicity receptors and their ligands, Immunol. Cell Biol. 92 (3) (Mar 2014) 221–229.
2
Editorial
A.
“ Natural Killer cells”
1975 1980 1985 1990 1995 2000 2005 2010 2015
B.
“NKcells”
[11] W. Leung, Infusions of allogeneic natural killer cells as cancer therapy, Clin. Cancer Res. 20 (13) (Jul 1 2014) 3390–3400. [12] L. Moretta, E. Montaldo, P. Vacca, G. Del Zotto, F. Moretta, P. Merli, F. Locatelli, M.C. Mingari, Human natural killer cells: origin, receptors, function, and clinical applications, Int. Arch. Allergy Immunol. 164 (4) (2014) 253–264. [13] T. Lysakova-Devine, C. O'Farrelly, Tissue-specific NK cell populations and their origin, J. Leukoc. Biol. 96 (6) (Dec 2014) 981–990. [14] M.G. Morvan, L.L. Lanier, NK cells and cancer: you can teach innate cells new tricks, Nat. Rev. Cancer 16 (1) (Jan 2016) 7–19. [15] Natural Killer Cell Adoptive Immunotherapy: Coming of Age. Dean Lee. [16] Alteration of NK cell phenotype and function in obese individuals. Sébastien Viel. [17] NK cell compartment in the peripheral blood and spleen in adult patients with primary immune thrombocytopenia. Frederic Vely. [18] Natural killer cell biology illuminated by primary immunodeficiency syndromes in humans. Yenan Bryceson. [19] Natural killer cells from psoriasis vulgaris patients have reduced levels of cytotoxicity associated degranulation and cytokine production. Clair M Gardiner. [20] Bench to bedside: NK cells and control of metastasis. Fernando Guimaraes [21] Transcriptional and post-transcriptional regulation of NK cell development and function. Todd Fehniger. [22] Quantification of Natural Killer Cell Polarization and Visualization of Synaptic Granule Externalization by Imaging Flow Cytometry. Emily Mace & Mark Smyth. [23] Adoptive Transfer of Natural Killer Cells Promotes the Anti-Tumor Efficacy of T Cells (MS & video). Per Basse.
Mark A. Exley E-mail address: [email protected] Jordan S. Orange
1975 1980 1985 1990 1995 2000 2005 2010 2015 Fig. 1. Citations in PubMed with ‘NK cells’ in Abstract, Title, &/or Keywords. A. Search used the terms “Natural Killer cells” recovered approximately 40,000 citations. B. Use of the exact phrase “NK cell(s)” produced about 1/2 as many (~20,000) citations with a more uniformly rising distribution.
[10] A.S. Chretien, A. Le Roy, N. Vey, T. Prebet, D. Blaise, C. Fauriat, D. Olive, CancerInduced Alterations of NK-Mediated Target Recognition: Current and Investigational Pharmacological Strategies Aiming at Restoring NK-Mediated Anti-Tumor Activity, Front. Immunol. 5 (Mar 24 2014) 122.