Các dấu hiệu sinh học của hội chứng giải phóng cytokine và độc tính thần kinh liên quan đến liệu pháp tế bào CAR-T

First-Ever CAR. T-cell therapy approved in U.S. Cancer Discov; 2017. https://doi.org/10.1158/2159-8290.CD-NB2017-126. FDA Approves Second CAR T-cell Therapy. Cancer Discov; 2017. https://doi.org/10.1158/2159-8290.cd-nb2017-155. DeFrancesco L. CAR-T's forge ahead, despite Juno deaths. Nat Biotechnol. 2017;35:6–7. Teachey DT, Lacey SF, Shaw PA, Melenhorst JJ, Maude SL, Frey N, et al. Identification of predictive biomarkers for cytokine release syndrome after Chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Cancer Discov. 2016;6:664–79. Wang Z, Guo Y, Han W. Current status and perspectives of chimeric antigen receptor modified T cells for cancer treatment. Protein Cell; 2017. https://doi.org/10.1007/s13238-017-0400-z. Dai H, Wang Y, Lu X, Han W. Chimeric antigen receptors modified T-cells for cancer therapy. J Natl Cancer Inst. 2016;108:djv439. Brudno JN, Kochenderfer JN. Chimeric antigen receptor T-cell therapies for lymphoma. Nat Rev Clin Oncol; 2017. https://doi.org/10.1038/nrclinonc.2017.128. Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol; 2017. https://doi.org/10.1038/nrclinonc.2017.148. Buechner J, Grupp SA, Maude SL, Boyer M, Bittencourt H, Laetsch TW, et al. Global registration trial of efficacy and safety of CTL019 in pediatric and young adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL): update to the interim analysis. Clinical Lymphoma Myeloma Leuk. 2017;17:S263–4. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med; 2017. https://doi.org/10.1056/NEJMoa1707447. Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124:188–95. Fitzgerald JC, Weiss SL, Maude SL, Barrett DM, Lacey SF, Melenhorst JJ, et al. Cytokine release syndrome after Chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia. Crit Care Med. 2017;45:e124–31. Hay KA, Hanafi LA, Li D, Gust J, Liles WC, Wurfel MM, et al. Kinetics and biomarkers of severe cytokine release syndrome after CD19 Chimeric antigen receptor-modified T cell therapy. Blood; 2017. https://doi.org/10.1182/blood-2017-06-793141. Gust J, Hay KA, Hanafi LA, Li D, Myerson D, Gonzalez-Cuyar LF, et al. Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells. Cancer Discov. 2017;7:1404–19. Obstfeld AE, Frey NV, Mansfield K, Lacey SF, June CH, Porter DL, et al. Cytokine release syndrome associated with chimeric-antigen receptor T-cell therapy; clinicopathological insights. Blood. 2017; https://doi.org/10.1182/blood-2017-08-802413. Park JH, Santomasso B, Riviere I, Senechal B, Wang X, Purdon T, et al. Baseline and early post-treatment clinical and laboratory factors associated with severe neurotoxicity following 19-28z CAR T cells in adult patients with relapsed B-ALL. J Clin Oncol. 2017;35:7024. Frey N. Cytokine release syndrome: who is at risk and how to treat. Best Pract Res Clin Haematol. 2017;30:336–40. Schuster SJ, Bishop MR, Tam C, Waller EK, Borchmann P, McGuirk J, et al. Global pivotal phase 2 trial of the Cd19-targeted therapy Ctl019 in adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (Dlbcl)-an interim analysis. Hematol Oncol. 2017;35:27. Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017;129:3322–31. Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak Ö, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med; 2017. https://doi.org/10.1056/NEJMoa1708566. DeAngelo DJ, Ghobadi A, Park JH, Dinner SN, Mannis GN, Lunning MA, et al. 32nd Annual Meeting and Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2017): Part One National Harbor, MD, USA. 8-12 November 2017 Abstracts. J Immunother Cancer. 2017;5(Suppl 2):P217. Abramson JS, Palomba ML, Gordon LI, Lunning MA, Arnason JE, Wang M, et al. High durable CR rates in relapsed/refractory (R/R) aggressive B-NHL treated with the CD19-directed CAR T cell product JCAR017 (TRANSCEND NHL 001): defined composition allows for dose-finding and definition of pivotal cohort. Blood. 2017;130:581. Hu Y, Wu Z, Yu J, Wang J, Wei G, Wu W, et al. Efficacy of CD19-targeted chimeric antigen receptor T cells in the treatment of relapsed extramedullary B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). J Clin Oncol. 2017;35:–e14549. Xiao L, Huang H, Huang X, Ke X, Hu Y, Li J, et al. Efficacy of anti-CD19 chimeric antigen receptor modified T(CAR-T) cell therapy in Chinese patients with relapsed/refractory acute lymphocytic leukemia in a multicenter trial. J Clin Oncol. 2017;35:7028. Wang Y, Chen M, Wu Z, Tong C, Huang J, Lv H, et al. CD133-redirected chimeric antigen receptor engineered autologous T-cell treatment in patients with advanced and metastatic malignancies. J Clin Oncol. 2017;35:3042. Yescarta (axicabtagene ciloleucel) suspension for intravenous infusion prescribing information, Kite Pharma, Inc, October 2017. Available at https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm581222.htm. Accessed 7 Nov 2017. Kymriah (tisagenlecleucel) suspension for intravenous infusion prescribing information, Novartis Pharmaceuticals Corp; 2017. Available at www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM573941.pdf. Accessed 6 Sept 2017. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–17. Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014;6:224ra225. Mei H, Jiang H, Wu Y, Guo T, Xia L, Jin R, et al. Neurological toxicities and coagulation disorders in the cytokine release syndrome during CAR-T therapy. Br J Haematol; 2017. https://doi.org/10.1111/bjh.14680. Dai H, Zhang W, Li X, Han Q, Guo Y, Zhang Y, et al. Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia. Oncoimmunology. 2015;4:e1027469. Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016;127:3321–30. Ishii K, Shalabi H, Yates B, Delbrook C, Mackall CL, Fry TJ, et al. Tocilizumab-refractory cytokine release syndrome (CRS) triggered by Chimeric antigen receptor (CAR)-Transduced T cells may have distinct cytokine profiles compared to typical CRS. Blood. 2016;128:3358. Mueller KT, Maude SL, Porter DL, Frey N, Wood P, Han X, et al. Cellular kinetics of CTL019 in relapsed/refractory B-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia. Blood; 2017. https://doi.org/10.1182/blood-2017-06-786129. Frey NV, Levine BL, Lacey SF, Grupp SA, Maude SL, Schuster SJ, et al. Refractory cytokine release syndrome in recipients of Chimeric antigen receptor (CAR) T cells. Blood. 2014;124:2296. Xu XJ, Tang YM. Cytokine release syndrome in cancer immunotherapy with chimeric antigen receptor engineered T cells. Cancer Lett. 2014;343:172–8. Zhang Y, Zhang W, Dai H, Wang Y, Shi F, Wang C, et al. An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T (CAR-T) cells. Sci China Life Sci. 2016;59:379–85. Wang CM, Wu ZQ, Wang Y, Guo YL, Dai HR, Wang XH, et al. Autologous T cells expressing CD30 Chimeric antigen receptors for relapsed or refractory Hodgkin lymphoma: an open-label phase I trial. Clin Cancer Res. 2017;23:1156–66. O'Hara MH, Stashwick C, Plesa G, Tanyi JL. Overcoming barriers of car T-cell therapy in patients with mesothelin-expressing cancers. Immunotherapy. 2017;9:767–80. Brentjens R, Yeh R, Bernal Y, Riviere I, Sadelain M. Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverse event in a phase I clinical trial. Mol Ther. 2010;18:666–8. Cai B, Guo M, Wang Y, Zhang Y, Yang J, Guo Y, et al. Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia. J Hematol Oncol. 2016;9:131. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA et al. T Cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet (London Engl). 2015; 385:517-528. Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA, Loren AW, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7:303ra139. Frey NV, Porter DL. Cytokine release syndrome with novel therapeutics for acute lymphoblastic leukemia. Hematol Am Soc Hematol Educ Program. 2016;2016:567–72. Norman DJ, Chatenoud L, Cohen D, Goldman M. Consensus statement regarding OKT3-induced cytokine-release syndrome and human antimouse antibodies. Transplant Proc. 1993;25:89–92. Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood. 1999;94:2217–24. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006;355:1018–28. Wing MG, Moreau T, Greenwood J, Smith RM, Hale G, Isaacs J, et al. Mechanism of first-dose cytokine-release syndrome by CAMPATH 1-H: involvement of CD16 (FcgammaRIII) and CD11a/CD18 (LFA-1) on NK cells. J Clin Invest. 1996;98:2819–26. Teachey DT, Rheingold SR, Maude SL, Zugmaier G, Barrett DM, Seif AE, et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 2013;121:5154–7. Rotz SJ, Leino D, Szabo S, Mangino JL, Turpin BK, Pressey JG. Severe cytokine release syndrome in a patient receiving PD-1-directed therapy. Pediatr Blood Cancer; 2017. https://doi.org/10.1002/pbc.26642. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76:16–32. Bugelski PJ, Achuthanandam R, Capocasale RJ, Treacy G, Bouman-Thio E. Monoclonal antibody-induced cytokine-release syndrome. Expert Rev Clin Immunol. 2009;5:499–521. Walker M, Makropoulos D, Achuthanandam R, Bugelski PJ. Recent advances in the understanding of drug-mediated infusion reactions and cytokine release syndrome. Curr Opin Drug Discov Devel. 2010;13:124–35. Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest. 2000;117:1162–72. Balkwill FR, Burke F. The cytokine network. Immunol Today. 1989;10:299–304. Yiu HH, Graham AL, Stengel RF. Dynamics of a cytokine storm. PLoS One. 2012;7:e45027. Harris DT, Kranz DM. Adoptive T cell therapies: a comparison of T cell receptors and Chimeric antigen receptors. Trends Pharmacol Sci. 2016;37:220–30. Yang Y, Kohler ME, Chien CD, Sauter CT, Jacoby E, Yan C, et al. TCR engagement negatively affects CD8 but not CD4 CAR T cell expansion and leukemic clearance. Sci Transl Med; 2017. https://doi.org/10.1126/scitranslmed.aag1209. Adusumilli PS, Cherkassky L, Villena-Vargas J, Colovos C, Servais E, Plotkin J, et al. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med. 2014;6:261ra151. Wu C, Xue Y, Wang P, Lin L, Liu Q, Li N, et al. IFN-γ primes macrophage activation by increasing Phosphatase and Tensin homolog via Downregulation of miR-3473b. J Immunol. 2014;193:3036–44. Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol. 2009;27:451–83. Prudent V, Breitbart WS. Chimeric antigen receptor T-cell neuropsychiatric toxicity in acute lymphoblastic leukemia. Palliat Support Care. 2017;15:499–503. Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM, Ramakrishna S, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med; 2017. https://doi.org/10.1038/nm.4441. Hawkes N. Trial of novel leukaemia drug is stopped for second time after two more deaths. BMJ. 2016;355:i6376. Abbasi J, Amid FDA. Approval filings, another CAR-T therapy patient death. JAMA. 2017;317:2271. Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16:57. Wu J, Fu J, Zhang M, Liu D. Blinatumomab: a bispecific T cell engager (BiTE) antibody against CD19/CD3 for refractory acute lymphoid leukemia. J Hematol Oncol. 2015;8:104. Fan G, Wang Z, Hao M, Li J. Bispecific antibodies and their applications. J Hematol Oncol. 2015;8:130. O’Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K, Morrissette JJD, et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med; 2017. https://doi.org/10.1126/scitranslmed.aaa0984. Abramson JS, McGree B, Noyes S, Plummer S, Wong C, Chen YB, et al. Anti-CD19 CAR T cells in CNS diffuse large-B-cell lymphoma. N Engl J Med. 2017;377:783–4. Hu Y, Sun J, Wu Z, Yu J, Cui Q, Pu C, et al. Predominant cerebral cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy. J Hematol Oncol. 2016;9:70. Mackall CL, Miklos DB. CNS endothelial cell activation emerges as a driver of CAR T cell-associated neurotoxicity. Cancer Discov. 2017;7:1371–3. Kometani H, Kawatani M, Ohta G, Okazaki S, Ogura K, Yasutomi M, et al. Marked elevation of interleukin-6 in mild encephalopathy with a reversible splenial lesion (MERS) associated with acute focal bacterial nephritis caused by Enterococcus faecalis. Brain and Development. 2014;36:551–3. Inman S. JCAR015 Experience Informs Future CAR-T Studies. OncLive; 2017. http://www.onclive.com/web-exclusives/jcar015-experience-informs-future-cart-studies. Accessed 10 Nov 2017. Turtle CJ, Hay KA, Hanafi LA, Li D, Cherian S, Chen X, et al. Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific Chimeric antigen receptor-modified T cells after failure of Ibrutinib. J Clin Oncol. 2017;35:3010–20. Turtle CJ, Hanafi LA, Berger C, Gooley TA, Cherian S, Hudecek M, et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest. 2016;126:2123–38. Wang Y, Zhang WY, Han QW, Liu Y, Dai HR, Guo YL, et al. Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol. 2014;155:160–75. Rouce RH, Heslop HE. Forecasting cytokine storms with new predictive biomarkers. Cancer Discov. 2016;6:579–80. Zhang W-y, Wang Y, Guo Y-l, Dai H-r, Yang Q-m, Zhang Y-j, et al. Treatment of CD20-directed Chimeric antigen receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report. Signal Transduct Target Ther. 2016;1:16002. Turtle CJ, Hay KA, Gust J, Hanafi L-A, Li D, Liles WC, et al. Cytokine release syndrome (CRS) and neurotoxicity (NT) after CD19-specific chimeric antigen receptor- (CAR-) modified T cells. J Clin Oncol. 2017;35:3020. Park JH, Riviere I, Wang XY, Purdon T, Sadelain M, Brentjens RJ. Impact of disease burden on long-term outcome of 19-28z CAR modified T cells in adult patients with relapsed B-ALL. J Clin Oncol. 2016;34:7003. Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365:725–33. Feng K, Liu Y, Guo Y, Qiu J, Wu Z, Dai H, et al. Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers. Protein Cell; 2017. https://doi.org/10.1007/s13238-017-0440-4. Turtle CJ, Hanafi LA, Berger C, Hudecek M, Pender B, Robinson E, et al. Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med. 2016;8:355ra116. Xu Y, Zhang M, Ramos CA, Durett A, Liu E, Dakhova O, et al. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Blood. 2014;123:3750–9. Hoyos V, Savoldo B, Quintarelli C, Mahendravada A, Zhang M, Vera J, et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma|[sol]|leukemia effects and safety. Leukemia. 2010;24:1160. Waldmann TA. Interleukin-15 in the treatment of cancer. Expert Rev Clin Immunol. 2014;10:1689. Kochenderfer JN, Somerville RPT, Lu T, Shi V, Bot A, Rossi J, et al. Lymphoma remissions caused by anti-CD19 Chimeric antigen receptor T cells are associated with high serum Interleukin-15 levels. J Clin Oncol. 2017;35:1803–13. Turtle CJ, Hay KA, Juliane G, Hanafi LA, Li D, Chaney C, et al. Biomarkers of cytokine release syndrome and neurotoxicity after CD19 CAR-T cells and mitigation of toxicity by cell dose. Blood. 2016;128:1852. Gardner R, Leger KJ, Annesley CE, Summers C, Rivers J, Gust J, et al. Decreased rates of severe CRS seen with early intervention strategies for CD19 CAR-T cell toxicity management. Blood. 2016;128:586. Locke FL, Neelapu SS, Bartlett NL, Lekakis LJ, Jacobson CA, Braunschweig I, et al. Preliminary results of prophylactic Tocilizumab after Axicabtageneciloleucel (axi-cel; KTE-C19) treatment for patients with Refractory,Aggressive non-Hodgkin lymphoma (NHL). Blood. 2017;130:–1547. Wang Z, Wu Z, Liu Y, Han W. New development in CAR-T cell therapy. J Hematol Oncol. 2017;10:53. Lichtman EI, Dotti G. Chimeric antigen receptor T-cells for B-cell malignancies. Transl Res; 2017. https://doi.org/10.1016/j.trsl.2017.06.011. Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011;365:1673–83. Wang X, Chang WC, Wong CW, Colcher D, Sherman M, Ostberg JR, et al. A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood. 2011;118:1255–63. Philip B, Kokalaki E, Mekkaoui L, Thomas S, Straathof K, Flutter B, et al. A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood. 2014;124:1277–87. Qasim W, Zhan H, Samarasinghe S, Adams S, Amrolia P, Stafford S, et al. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med; 2017. https://doi.org/10.1126/scitranslmed.aaj2013.