Células asesinas naturales con el receptor de antígeno quimérico (CAR-NK): terapia emergente contra el cáncer
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Vázquez Rodríguez, A., & Mendoza-Rincón, J. (2021). Células asesinas naturales con el receptor de antígeno quimérico (CAR-NK): terapia emergente contra el cáncer. NOVA, 19(37), 11-24. https://doi.org/10.22490/24629448.5472
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Autores
Adrián Vázquez Rodríguez
Jorge Flavio Mendoza-Rincón
Resumen
Una de las herramientas más novedosas en inmunoterapias adoptivas contra leucemias y tumores malignos es el uso del receptor de antígeno quimérico “CAR”. El receptor CAR ha sido ampliamente utilizada en células T (células CAR-T) potenciando su eficacia en el reconocimiento y eliminación de tumores, obteniéndose a la fecha terapias basadas en esta tecnología. No obstante, las células CAR-T llegan a repercutir negativamente en la salud del paciente, presentando el síndrome neurológico de efecto inmune asociado a células (ICANS) y el síndrome de lanzamiento de citocinas (SLC). Como consecuencia,
el paciente necesita ser hospitalizado durante la terapia. Además, el coste de manufactura y terapia es elevado, siendo una tecnología limitada a un sector muy bajo de la población. En este trabajo, mencionamos el empleo de una terapia emergente de células asesinas naturales (NK) con el receptor CAR (CAR-NK), que cuentan con muchas ventajas por encima de las células CAR-T. Las células CAR-NK conservan su capacidad citotóxica en contra de tumores gracias a su acción dependiente de receptores activadores e inhibidores, por lo que el receptor CAR, solo estimula sus habilidades y persistencia. Sumado a esto, el
coste de una terapia de células CAR-NK podría resultar redituable debido a la capacidad de las células CAR-NK de eliminar múltiples células tumorales sin generar daño colateral en el paciente. Aquí analizamos las características de los múltiples receptores CAR y los fenotipos de células NK que han sido utilizados durante múltiples ensayos (NK-92, células NK de sangre cordal y periférica, y células NK iPSC).
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NOVA por http://www.unicolmayor.edu.co/publicaciones/index.php/nova se distribuye bajo una Licencia Creative Commons Atribución-NoComercial-SinDerivar 4.0 Internacional.
Así mismo, los autores mantienen sus derechos de propiedad intelectual sobre los artículos.
Referencias
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11. Chmielewski M, Abken H. TRUCKs: the fourth generation of CARs. Expert Opin Biol Ther. 2015;15(8):1145-54. doi: 10.1517/14712598.2015.1046430.
12. Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, et al. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. N Engl J Med. 2020;382(6):545-553. doi: 10.1056/NEJMoa1910607.
13. Daher M, Rezvani K. Outlook for New CAR-Based Therapies with a Focus on CAR NK Cells: What Lies Beyond CAR-Engineered T Cells in the Race against Cancer. Cancer Discov. 2021;11(1):45-58. doi: 10.1158/2159-8290.CD-20-0556.
14. Krause A, Guo HF, Latouche JB, Tan C, Cheung NK, Sadelain M. Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes. J Exp Med. 1998;188(4):619-26. doi: 10.1084/jem.188.4.619.
15. Eshhar Z, Waks T, Bendavid A, Schindler DG. Functional expression of chimeric receptor genes in human T cells. J Immunol Methods. 2001;248(1-2):67-76. doi: 10.1016/s0022-1759(00)00343-4.
16. Milone MC, Fish JD, Carpenito C, Carroll RG, Binder GK, Teachey D, et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther. 2009;17(8):1453-64. doi: 10.1038/mt.2009.83.
17. Till BG, Jensen MC, Wang J, Qian X, Gopal AK, Maloney DG, et al. CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results. Blood. 2012;119(17):3940-50. doi: 10.1182/blood-2011-10-387969.
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19. Bollino D, Webb TJ. Chimeric antigen receptor-engineered natural killer and natural killer T cells for cancer immunotherapy. Transl Res. 2017;187:32-43. doi: 10.1016/j.trsl.2017.06.003.
20. Bear AS, Morgan RA, Cornetta K, June CH, Binder-Scholl G, Dudley ME, et al. Replication-competent retroviruses in gene-modified T cells used in clinical trials: is it time to revise the testing requirements? Mol Ther. 2012;20(2):246-9. doi: 10.1038/mt.2011.288.
21. Zhang C, Burger MC, Jennewein L, Genßler S, Schönfeld K, Zeiner P, et al. ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma. J Natl Cancer Inst. 2015;108(5). doi: 10.1093/jnci/djv375.
22. MacLeod RA, Nagel S, Kaufmann M, Greulich-Bode K, Drexler HG. Multicolor-FISH analysis of a natural killer cell line (NK-92). Leuk Res. 2002;26(11):1027-33. doi: 10.1016/s0145-2126(02)00055-3.
23. André P, Denis C, Soulas C, Bourbon-Caillet C, Lopez J, Arnoux T, et al. Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells. Cell. 2018;175(7):1731-1743.e13. doi: 10.1016/j.cell.2018.10.014.
24. Kamiya T, Seow SV, Wong D, Robinson M, Campana D. Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells. J Clin Invest. 2019;129(5):2094-2106. doi: 10.1172/JCI123955.
25. Björklund AT, Carlsten M, Sohlberg E, Liu LL, Clancy T, Karimi M, et al. Complete Remission with Reduction of High-Risk Clones following Haploidentical NK-Cell Therapy against MDS and AML. Clin Cancer Res. 2018;24(8):1834-1844. doi: 10.1158/1078-0432.CCR-17-3196.
26. Knorr DA, Ni Z, Hermanson D, Hexum MK, Bendzick L, Cooper LJ, et al. Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy. Stem Cells Transl Med. 2013;2(4):274-83. doi: 10.5966/sctm.2012-0084.
27. Valamehr B, Robinson M, Abujarour R, Rezner B, Vranceanu F, Le T, et al. Platform for induction and maintenance of transgene-free hiPSCs resembling ground state pluripotent stem cells. Stem Cell Reports. 2014;2(3):366-81. doi: 10.1016/j.stemcr.2014.01.014.
28. Saetersmoen ML, Hammer Q, Valamehr B, Kaufman DS, Malmberg KJ. Off-the-shelf cell therapy with induced pluripotent stem cell-derived natural killer cells. Semin Immunopathol. 2019;41(1):59-68. doi: 10.1007/s00281-018-0721-x.
29. Kruschinski A, Moosmann A, Poschke I, Norell H, Chmielewski M, Seliger B, et al. Engineering antigen-specific primary human NK cells against HER-2 positive carcinomas. Proc Natl Acad Sci U S A. 2008;105(45):17481-6. doi: 10.1073/pnas.0804788105.
30. Han J, Chu J, Keung Chan W, Zhang J, Wang Y, Cohen JB, et al. CAR-Engineered NK Cells Targeting Wild-Type EGFR and EGFRvIII Enhance Killing of Glioblastoma and Patient-Derived Glioblastoma Stem Cells. Sci Rep. 2015;5:11483. doi: 10.1038/srep11483.
31. MacKay M, Afshinnekoo E, Rub J, Hassan C, Khunte M, Baskaran N, et al. The therapeutic landscape for cells engineered with chimeric antigen receptors. Nat Biotechnol. 2020;38(2):233-244. doi: 10.1038/s41587-019-0329-2.
32. Hanenberg H, Xiao XL, Dilloo D, Hashino K, Kato I, Williams DA. Colocalization of retrovirus and target cells on specific fibronectin fragments increases genetic transduction of mammalian cells. Nat Med. 1996;2(8):876-82. doi: 10.1038/nm0896-876.
33. Davis HE, Morgan JR, Yarmush ML. Polybrene increases retrovirus gene transfer efficiency by enhancing receptor-independent virus adsorption on target cell membranes. Biophys Chem. 2002;97(2-3):159-72. doi: 10.1016/s0301-4622(02)00057-1.
34. Xiao L, Cen D, Gan H, Sun Y, Huang N, Xiong H, et al. Adoptive Transfer of NKG2D CAR mRNA-Engineered Natural Killer Cells in Colorectal Cancer Patients. Mol Ther. 2019;27(6):1114-1125. doi: 10.1016/j.ymthe.2019.03.011.
35. Rostovskaya M, Fu J, Obst M, Baer I, Weidlich S, Wang H, et al. Transposon-mediated BAC transgenesis in human ES cells. Nucleic Acids Res. 2012;40(19):e150. doi: 10.1093/nar/gks643.
36. Kebriaei P, Izsvák Z, Narayanavari SA, Singh H, Ivics Z. Gene Therapy with the Sleeping Beauty Transposon System. Trends Genet. 2017;33(11):852-870. doi: 10.1016/j.tig.2017.08.008.
2. Habib S, Tariq SM, Tariq M. Chimeric Antigen Receptor-Natural Killer Cells: The Future of Cancer Immunotherapy. Ochsner J. 2019;19(3):186-187. doi: 10.31486/toj.19.0033.
3. Daher M, Basar R, Gokdemir E, Baran N, Uprety N, Nunez Cortes AK, et al. Targeting a cytokine checkpoint enhances the fitness of armored cord blood CAR-NK cells. Blood. 2021;137(5):624-636. doi: 10.1182/blood.2020007748.
4. Daher M, Rezvani K. Next generation natural killer cells for cancer immunotherapy: the promise of genetic engineering. Curr Opin Immunol. 2018;51:146-153. doi: 10.1016/j.coi.2018.03.013.
5. Pfefferle A, Huntington ND. You Have Got a Fast CAR: Chimeric Antigen Receptor NK Cells in Cancer Therapy. Cancers (Basel). 2020;12(3):706. doi: 10.3390/cancers12030706.
6. Glienke W, Esser R, Priesner C, Suerth JD, Schambach A, Wels WS, et al. Advantages and applications of CAR-expressing natural killer cells. Front Pharmacol. 2015;6:21. doi: 10.3389/fphar.2015.00021.
7. Sadelain M, Brentjens R, Rivière I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013;3(4):388-98. doi: 10.1158/2159-8290.CD-12-0548
8. Barrett DM, Singh N, Porter DL, Grupp SA, June CH. Chimeric antigen receptor therapy for cancer. Annu Rev Med. 2014;65:333-47. doi: 10.1146/annurev-med-060512-150254.
9. Stone JD, Chervin AS, Kranz DM. T-cell receptor binding affinities and kinetics: impact on T-cell activity and specificity. Immunology. 2009;126(2):165-76. doi: 10.1111/j.1365-2567.2008.03015.x.
10. Bridgeman JS, Hawkins RE, Hombach AA, Abken H, Gilham DE. Building better chimeric antigen receptors for adoptive T cell therapy. Curr Gene Ther. 2010;10(2):77-90. doi: 10.2174/156652310791111001.
11. Chmielewski M, Abken H. TRUCKs: the fourth generation of CARs. Expert Opin Biol Ther. 2015;15(8):1145-54. doi: 10.1517/14712598.2015.1046430.
12. Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, et al. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. N Engl J Med. 2020;382(6):545-553. doi: 10.1056/NEJMoa1910607.
13. Daher M, Rezvani K. Outlook for New CAR-Based Therapies with a Focus on CAR NK Cells: What Lies Beyond CAR-Engineered T Cells in the Race against Cancer. Cancer Discov. 2021;11(1):45-58. doi: 10.1158/2159-8290.CD-20-0556.
14. Krause A, Guo HF, Latouche JB, Tan C, Cheung NK, Sadelain M. Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes. J Exp Med. 1998;188(4):619-26. doi: 10.1084/jem.188.4.619.
15. Eshhar Z, Waks T, Bendavid A, Schindler DG. Functional expression of chimeric receptor genes in human T cells. J Immunol Methods. 2001;248(1-2):67-76. doi: 10.1016/s0022-1759(00)00343-4.
16. Milone MC, Fish JD, Carpenito C, Carroll RG, Binder GK, Teachey D, et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther. 2009;17(8):1453-64. doi: 10.1038/mt.2009.83.
17. Till BG, Jensen MC, Wang J, Qian X, Gopal AK, Maloney DG, et al. CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results. Blood. 2012;119(17):3940-50. doi: 10.1182/blood-2011-10-387969.
18. Cairo MS, Coiffier B, Reiter A, Younes A; TLS Expert Panel. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010;149(4):578-86. doi: 10.1111/j.1365-2141.2010.08143.x.
19. Bollino D, Webb TJ. Chimeric antigen receptor-engineered natural killer and natural killer T cells for cancer immunotherapy. Transl Res. 2017;187:32-43. doi: 10.1016/j.trsl.2017.06.003.
20. Bear AS, Morgan RA, Cornetta K, June CH, Binder-Scholl G, Dudley ME, et al. Replication-competent retroviruses in gene-modified T cells used in clinical trials: is it time to revise the testing requirements? Mol Ther. 2012;20(2):246-9. doi: 10.1038/mt.2011.288.
21. Zhang C, Burger MC, Jennewein L, Genßler S, Schönfeld K, Zeiner P, et al. ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma. J Natl Cancer Inst. 2015;108(5). doi: 10.1093/jnci/djv375.
22. MacLeod RA, Nagel S, Kaufmann M, Greulich-Bode K, Drexler HG. Multicolor-FISH analysis of a natural killer cell line (NK-92). Leuk Res. 2002;26(11):1027-33. doi: 10.1016/s0145-2126(02)00055-3.
23. André P, Denis C, Soulas C, Bourbon-Caillet C, Lopez J, Arnoux T, et al. Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells. Cell. 2018;175(7):1731-1743.e13. doi: 10.1016/j.cell.2018.10.014.
24. Kamiya T, Seow SV, Wong D, Robinson M, Campana D. Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells. J Clin Invest. 2019;129(5):2094-2106. doi: 10.1172/JCI123955.
25. Björklund AT, Carlsten M, Sohlberg E, Liu LL, Clancy T, Karimi M, et al. Complete Remission with Reduction of High-Risk Clones following Haploidentical NK-Cell Therapy against MDS and AML. Clin Cancer Res. 2018;24(8):1834-1844. doi: 10.1158/1078-0432.CCR-17-3196.
26. Knorr DA, Ni Z, Hermanson D, Hexum MK, Bendzick L, Cooper LJ, et al. Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy. Stem Cells Transl Med. 2013;2(4):274-83. doi: 10.5966/sctm.2012-0084.
27. Valamehr B, Robinson M, Abujarour R, Rezner B, Vranceanu F, Le T, et al. Platform for induction and maintenance of transgene-free hiPSCs resembling ground state pluripotent stem cells. Stem Cell Reports. 2014;2(3):366-81. doi: 10.1016/j.stemcr.2014.01.014.
28. Saetersmoen ML, Hammer Q, Valamehr B, Kaufman DS, Malmberg KJ. Off-the-shelf cell therapy with induced pluripotent stem cell-derived natural killer cells. Semin Immunopathol. 2019;41(1):59-68. doi: 10.1007/s00281-018-0721-x.
29. Kruschinski A, Moosmann A, Poschke I, Norell H, Chmielewski M, Seliger B, et al. Engineering antigen-specific primary human NK cells against HER-2 positive carcinomas. Proc Natl Acad Sci U S A. 2008;105(45):17481-6. doi: 10.1073/pnas.0804788105.
30. Han J, Chu J, Keung Chan W, Zhang J, Wang Y, Cohen JB, et al. CAR-Engineered NK Cells Targeting Wild-Type EGFR and EGFRvIII Enhance Killing of Glioblastoma and Patient-Derived Glioblastoma Stem Cells. Sci Rep. 2015;5:11483. doi: 10.1038/srep11483.
31. MacKay M, Afshinnekoo E, Rub J, Hassan C, Khunte M, Baskaran N, et al. The therapeutic landscape for cells engineered with chimeric antigen receptors. Nat Biotechnol. 2020;38(2):233-244. doi: 10.1038/s41587-019-0329-2.
32. Hanenberg H, Xiao XL, Dilloo D, Hashino K, Kato I, Williams DA. Colocalization of retrovirus and target cells on specific fibronectin fragments increases genetic transduction of mammalian cells. Nat Med. 1996;2(8):876-82. doi: 10.1038/nm0896-876.
33. Davis HE, Morgan JR, Yarmush ML. Polybrene increases retrovirus gene transfer efficiency by enhancing receptor-independent virus adsorption on target cell membranes. Biophys Chem. 2002;97(2-3):159-72. doi: 10.1016/s0301-4622(02)00057-1.
34. Xiao L, Cen D, Gan H, Sun Y, Huang N, Xiong H, et al. Adoptive Transfer of NKG2D CAR mRNA-Engineered Natural Killer Cells in Colorectal Cancer Patients. Mol Ther. 2019;27(6):1114-1125. doi: 10.1016/j.ymthe.2019.03.011.
35. Rostovskaya M, Fu J, Obst M, Baer I, Weidlich S, Wang H, et al. Transposon-mediated BAC transgenesis in human ES cells. Nucleic Acids Res. 2012;40(19):e150. doi: 10.1093/nar/gks643.
36. Kebriaei P, Izsvák Z, Narayanavari SA, Singh H, Ivics Z. Gene Therapy with the Sleeping Beauty Transposon System. Trends Genet. 2017;33(11):852-870. doi: 10.1016/j.tig.2017.08.008.
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