본문 바로가기
KERD
논문KCI 등재

Development of Bispecific Antibody for Cancer Immunotherapy: Focus on T Cell Engaging Antibody

이승우|박윤지|김대희|문다인|Tae Nara
대한면역학회 (The Korean Association of Immunologists)|2022.02|Immune Network|제22권 제1호|pp. 1-22|DOI 10.4110/in.2022.22.e4

2

조회

0

다운로드

4

인용

0

참고문헌

키워드

Bispecific antibodiesCancer immunotherapyAdverse effectsBlinatumomabT cell engagerChimeric antigen receptor T cell therapy

초록

In the era of immunotherapeutic control of cancers, many advances in biotechnology, especially in Ab engineering, have provided multiple new candidates as therapeutic immuno-oncology modalities. Bispecific Abs (BsAbs) that recognize 2 different antigens in one molecule are promising drug candidates and have inspired an upsurge in research in both academia and the pharmaceutical industry. Among several BsAbs, T cell engaging BsAb (TCEB), a new class of therapeutic agents designed to simultaneously bind to T cells and tumor cells via tumor cell specific antigens in immunotherapy, is the most promising BsAb. Herein, we are providing an overview of the current status of the development of TCEBs. The diverse formats and characteristics of TCEBs, in addition to the functional mechanisms of BsAbs are discussed. Several aspects of a new TCEB-Blinatumomab-are reviewed, including the current clinical data, challenges of patient treatment, drawbacks regarding toxicities, and resistance of TCEB therapy. Development of the next generation of TCEBs is also discussed in addition to the comparison of TCEB with current chimeric antigen receptor-T therapy.

Abstract

In the era of immunotherapeutic control of cancers, many advances in biotechnology, especially in Ab engineering, have provided multiple new candidates as therapeutic immuno-oncology modalities. Bispecific Abs (BsAbs) that recognize 2 different antigens in one molecule are promising drug candidates and have inspired an upsurge in research in both academia and the pharmaceutical industry. Among several BsAbs, T cell engaging BsAb (TCEB), a new class of therapeutic agents designed to simultaneously bind to T cells and tumor cells via tumor cell specific antigens in immunotherapy, is the most promising BsAb. Herein, we are providing an overview of the current status of the development of TCEBs. The diverse formats and characteristics of TCEBs, in addition to the functional mechanisms of BsAbs are discussed. Several aspects of a new TCEB-Blinatumomab-are reviewed, including the current clinical data, challenges of patient treatment, drawbacks regarding toxicities, and resistance of TCEB therapy. Development of the next generation of TCEBs is also discussed in addition to the comparison of TCEB with current chimeric antigen receptor-T therapy.

참고문헌 (129)

  1. NisonoffA, "Recombination of a mixture of univalent antibody fragments of different specificity", Arch Biochem Biophys, 93, pp.460~462 (1961)
  2. Fudenberg HH, "Serologic demonstration of dual specificity of rabbit bivalent hybrid antibody", J Exp Med, 119, pp.151~166 (1964)
  3. Köhler G, "Continuous cultures of fused cells secreting antibody of predefined specificity", Nature, 256, pp.495~497 (1975)
  4. Milstein C, "Hybrid hybridomas and their use in immunohistochemistry", Nature, 305, pp.537~540 (1983)
  5. Suresh MR, "Advantages of bispecific hybridomas in one-step immunocytochemistry and immunoassays", Proc Natl Acad Sci U S A, 83, pp.7989~7993 (1986)
  6. Lindhofer H, "Preferential species-restricted heavy", light chain pairing in rat, J Immunol, pp.1995, 155[DOI]
  7. Mezzanzanica D, "Human ovarian carcinoma lysis by cytotoxic T cells targeted by bispecific monoclonal antibodies : analysis of the antibody components", Int J Cancer, 41, pp.609~615 (1988)
  8. Brennan M, "Preparation of bispecific antibodies by chemical recombination of monoclonal immunoglobulin G1 fragments", Science, 229, pp.81~83 (1985)
  9. Huston JS, "Protein engineering of antibody binding sites : recovery of specific activity in an antidigoxin single-chain Fv analogue produced in Escherichia coli", Proc Natl Acad Sci U S A, 85, pp.5879~5883 (1988)
  10. Ridgway JB, "‘Knobs-into-holes’ engineering of antibody CH3 domains for heavy chain heterodimerization", Protein Eng, 9, pp.617~621 (1996)
  11. Linke R, "Catumaxomab : clinical development and future directions", MAbs, 2, pp.129~136 (2010)
  12. Brown P, "Blinatumomab for MRD+ B-ALL : the evidence strengthens", Blood, 131, pp.1497~1498 (2018)
  13. Gökbuget N, "Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia", Blood, 131, pp.1522~1531 (2018)
  14. Halford Z, "A systematic review of blinatumomab in the treatment of acute lymphoblastic leukemia : engaging an old problem with new solutions", Ann Pharmacother, 55, pp.1236~1253 (2021)
  15. Neijssen J, "Discovery of amivantamab(JNJ-61186372), a bispecific antibody targeting EGFR and MET", J Biol Chem, 296, pp.100641~ (2021)
  16. Park K, "Amivantamab in EGFR exon 20 insertion–mutated non–small-cell lung cancer progressing on platinum chemotherapy : initial results from the CHRYSALIS phase I study", J Clin Oncol, 39, pp.3391~3402 (2021)
  17. Romero D, "Amivantamab is effective in NSCLC harbouring EGFR exon 20 insertions", Nat Rev Clin Oncol, 18, pp.604~ (2021)
  18. Cheong HS, "Affinity enhancement of bispecific antibody against two different epitopes in the same antigen", Biochem Biophys Res Commun, 173, pp.795~800 (1990)
  19. Kontermann RE, "Dual targeting strategies with bispecific antibodies", MAbs, 4, pp.182~197 (2012)
  20. Robert B, "Tumor targeting with newly designed biparatopic antibodies directed against two different epitopes of the carcinoembryonic antigen(CEA)", Int J Cancer, 81, pp.285~291 (1999)
  21. Lu D, "Acquired antagonistic activity of a bispecific diabody directed against two different epitopes on vascular endothelial growth factor receptor 2", J Immunol Methods, 230, pp.159~171 (1999)
  22. Asokan M, "Bispecific antibodies targeting different epitopes on the HIV-1 envelope exhibit broad and potent neutralization", J Virol, 89, pp.12501~12512 (2015)
  23. Tan W, "A bispecific antibody against two different epitopes on hepatitis B surface antigen has potent hepatitis B virus neutralizing activity", MAbs, 5, pp.946~955 (2013)
  24. You G, "Bispecific antibodies: a smart arsenal for cancer immunotherapies", Vaccines(Basel), 9, pp.724~ (2021)
  25. Blanco B, "Bispecific immunomodulatory antibodies for cancer immunotherapy", Clin Cancer Res, 27, pp.5457~5464 (2021)
  26. Hummel HD, "Phase I study of pasotuxizumab (AMG 212", BAY 2010112), a PSMA-targeting BiTE (bispecific T-cell engager) immune therapy for metastatic castration-resistant prostate cancer (mCRPC), 2020, pp.38(6_suppl), 124~
  27. Tran B, "609O results from a phase I study of AMG 160, a half-life extended(HLE), PSMA-targeted, bispecific T-cell engager(BiTE®)immune therapy for metastatic castration-resistant prostate cancer(mCRPC)", Ann Oncol, 31, pp.S507~ (2020)
  28. Rosenthal MA, "ATIM-49 (LTBK-01). AMG 596, a novel anti-EGFRvIII bispecific T cell engager (BiTE®) molecule for the treatment of glioblastoma (GBM): planned interim analysis in recurrent GBM (rGBM)", Neuro Oncol, 21(Supplement_6), pp.vi283~ (2019)
  29. Sternjak A, "Preclinical assessment of AMG 596, a bispecific T-cell engager(BiTE)immunotherapy targeting the tumor-specific antigen EGFRvIII", Mol Cancer Ther, 20, pp.925~933 (2021)
  30. Park JH, "Tumor hypoxia represses γδ T cell-mediated antitumor immunity against brain tumors", Nat Immunol, 22, pp.336~346 (2021)
  31. Oberg HH, "γδ T cell activation by bispecific antibodies", Cell Immunol, 296, pp.41~49 (2015)
  32. Ganesan R, "Selective recruitment of γδT cells by a bispecific antibody for the treatment of acute myeloid leukemia", Leukemia, 35, pp.2274~2284 (2021)
  33. Xie G, "CAR-NK cells : a promising cellular immunotherapy for cancer", EBioMedicine, 59, pp.102975~ (2020)
  34. Quatrini L, "Human NK cells, their receptors and function", Eur J Immunol, 51, pp.1566~1579 (2021)
  35. Schmohl JU, "Heterodimeric bispecific single chain variable fragments(scFv)killer engagers(BiKEs)enhance NK-cell activity against CD133+ colorectal cancer cells", Target Oncol, 11, pp.353~361 (2016)
  36. Reusing SB, "CD16xCD33 bispecific killer cell engager(BiKE)as potential immunotherapeutic in pediatric patients with AML and biphenotypic ALL", Cancer Immunol Immunother, 70, pp.3701~3708 (2021)
  37. Bogen JP, "Design of a trispecific checkpoint inhibitor and natural killer cell engager based on a 2 + 1 common light chain antibody architecture", Front Immunol, 12, pp.669496~ (2021)
  38. Cheng Y, "Trispecific killer engager 161519enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers", Cancer Biol Med, 17, pp.1026~1038 (2020)
  39. Jörg U. Schmohl, "Engineering of Anti-CD133 Trispecific Molecule Capable of Inducing NK Expansion and Driving Antibody-Dependent Cell-Mediated Cytotoxicity", Cancer Research and Treatment, 49(4), pp.1140~1152 (2017), 대한암학회
  40. Vallera DA, "A HER2 tri-specific NK cell engager mediates efficient targeting of human ovarian cancer", Cancers(Basel), 13, pp.3994~ (2021)
  41. Dovedi SJ, "Design and efficacy of a monovalent bispecific PD-1", CTLA4 antibody that enhances CTLA4 blockade on PD-1+ activated T cells, 2021, pp.11, 1100~1117
  42. Dovedi SJ, "Abstract 2776 : MEDI5752 : a novel bispecific antibody that preferentially targets CTLA-4 on PD-1expressing T-cells", Cancer Res, 78, pp.2776~ (2018)
  43. Anderson AC, "Lag-3, Tim-3, and TIGIT : co-inhibitory receptors with specialized functions in immune regulation", Immunity, 44, pp.989~1004 (2016)
  44. Deak LL, "Abstract 2270 : RG7769(PD1-TIM3), a novel heterodimeric avidity-driven T cell specific PD-1", TIM-3bispecific antibody lacking Fc-mediated effector functions for dual checkpoint inhibition to reactivate dysfunctional T cells, 2020, pp.80, 2270~
  45. Gaspar M, "CD137", OX40 bispecific antibody induces potent antitumor activity that is dependent on target coengagement, 2020, pp.8, 781~793
  46. Johnson M, "493 first-in-human phase 1", 2 trial to evaluate the safety and initial clinical activity of DuoBody®-CD40×4–1bb(GEN1042)in patients with advanced solid tumors, 2021, pp.9(Suppl 2), A525~
  47. Kvarnhammar AM, "The CTLA-4 x OX40 bispecific antibody ATOR-1015induces anti-tumor effects through tumor-directed immune activation", J Immunother Cancer, 7, pp.103~ (2019)
  48. Jeong S, "Novel anti-4-1BB×PD-L1 bispecific antibody augments anti-tumor immunity through tumor-directed T-cell activation and checkpoint blockade", J Immunother Cancer, 9, pp.e002428~ (2021)
  49. Park JA, "Potent ex vivo armed T cells using recombinant bispecific antibodies for adoptive immunotherapy with reduced cytokine release", J Immunother Cancer, 9, pp.e002222~ (2021)
  50. Yankelevich M, "Phase I study of OKT3 x hu3F8 bispecific antibody(GD2Bi)armed T cells(GD2BATs)in GD2-positive tumors", J Clin Oncol, 37(15_suppl), pp.2533~ (2019)
  51. Thakur A, "Bispecific antibody armed metabolically enhanced headless car T cells", Front Immunol, 12, pp.690437~ (2021)
  52. Liu H, "Fc engineering for developing therapeutic bispecific antibodies and novel scaffolds", Front Immunol, 8, pp.38~ (2017)
  53. Zhang J, "Development of bispecific antibodies in China : overview and prospects", Antib Ther, 3, pp.126~145 (2020)
  54. Stewart R, "The role of Fc gamma receptors in the activity of immunomodulatory antibodies for cancer", J Immunother Cancer, 2, pp.29~ (2014)
  55. Saunders KO, "Conceptual approaches to modulating antibody effector functions and circulation half-life", Front Immunol, 10, pp.1296~ (2019)
  56. You G, "B7-H3×4-1BB bispecific antibody augments antitumor immunity by enhancing terminally differentiated CD8+ tumorinfiltrating lymphocytes", Sci Adv, 7, pp.eaax3160~ (2021)
  57. Mlecnik B, "Tumor immunosurveillance in human cancers", Cancer Metastasis Rev, 30, pp.5~12 (2011)
  58. Zhang L, "Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer", N Engl J Med, 348, pp.203~213 (2003)
  59. Galon J, "Type, density, and location of immune cells within human colorectal tumors predict clinical outcome", Science, 313, pp.1960~1964 (2006)
  60. Wahlin BE, "CD8+ T-cell content in diagnostic lymph nodes measured by flow cytometry is a predictor of survival in follicular lymphoma", Clin Cancer Res, 13, pp.388~397 (2007)
  61. Zhu Z, "High level secretion of a humanized bispecific diabody from Escherichia coli", Biotechnology(N Y), 14, pp.192~196 (1996)
  62. Titus JA, "Human T cells targeted with anti-T3cross-linked to antitumor antibody prevent tumor growth in nude mice", J Immunol, 138, pp.4018~4022 (1987)
  63. Weiner GJ, "Bispecific anti-idiotype", anti-CD3 antibody therapy of murine B cell lymphoma, 1991, pp.147, 4035~4044
  64. Demanet C, "Bispecific antibody-mediated immunotherapy of the BCL1 lymphoma : increased efficacy with multiple injections and CD28-induced costimulation", Blood, 87, pp.4390~4398 (1996)
  65. Renner C, "Cure of xenografted human tumors by bispecific monoclonal antibodies and human T cells", Science, 264, pp.833~835 (1994)
  66. Kipriyanov SM, "Bispecific CD3 x CD19 diabody for T cell-mediated lysis of malignant human B cells", Int J Cancer, 77, pp.763~772 (1998)
  67. Cochlovius B, "Cure of Burkitt’s lymphoma in severe combined immunodeficiency mice by T cells, tetravalent CD3 x CD19tandem diabody, and CD28 costimulation", Cancer Res, 60, pp.4336~4341 (2000)
  68. Nitta T, "Preliminary trial of specific targeting therapy against malignant glioma", Lancet, 335, pp.368~371 (1990)
  69. Canevari S, "Regression of advanced ovarian carcinoma by intraperitoneal treatment with autologous T lymphocytes retargeted by a bispecific monoclonal antibody", J Natl Cancer Inst, 87, pp.1463~1469 (1995)
  70. Manzke O, "Locoregional treatment of low-grade B-cell lymphoma with CD3xCD19 bispecific antibodies and CD28 costimulation. I. Clinical phase I evaluation", Int J Cancer, 91, pp.508~515 (2001)
  71. Mack M, "A small bispecific antibody construct expressed as a functional singlechain molecule with high tumor cell cytotoxicity", Proc Natl Acad Sci U S A, 92, pp.7021~7025 (1995)
  72. Löffler A, "A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes", Blood, 95, pp.2098~2103 (2000)
  73. Kufer P, "Construction and biological activity of a recombinant bispecific single-chain antibody designed for therapy of minimal residual colorectal cancer", Cancer Immunol Immunother, 45, pp.193~197 (1997)
  74. Mack M, "Biologic properties of a bispecific single-chain antibody directed against 17-1A(EpCAM)and CD3 : tumor cell-dependent T cell stimulation and cytotoxic activity", J Immunol, 158, pp.3965~3970 (1997)
  75. Irvine DJ, "Function-specific variations in the immunological synapses formed by cytotoxic T cells", Proc Natl Acad Sci U S A, 100, pp.13739~13740 (2003)
  76. Portell CA, "Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia", Clin Pharmacol, 5, pp.5~11 (2013)
  77. Topp MS, "Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia", J Clin Oncol, 32, pp.4134~4140 (2014)
  78. Duell J, "Functionally defective T cells after chemotherapy of B-cell malignancies can be activated by the tetravalent bispecific CD19", CD3 antibody AFM11, 2019, pp.42, 180~188
  79. Frey NV, "Cytokine release syndrome with novel therapeutics for acute lymphoblastic leukemia", Hematology Am Soc Hematol Educ Program, 2016, pp.567~572 (2016)
  80. Teachey DT, "Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy", Blood, 121, pp.5154~5157 (2013)
  81. Aldoss I, "Cytokine release syndrome with the novel treatments of acute lymphoblastic leukemia : pathophysiology, prevention, and treatment", Curr Oncol Rep, 21, pp.4~ (2019)
  82. Barker CA, "Cytokine release syndrome after radiation therapy : case report and review of the literature", J Immunother Cancer, 6, pp.1~ (2018)
  83. Jung SH, "Efficacy and safety of blinatumomab treatment in adult Korean patients with relapsed", refractory acute lymphoblastic leukemia on behalf of the Korean Society of Hematology ALL Working Party, 2019, pp.98, 151~158
  84. Nägele V, "Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed", refractory ALL, 2017, pp.6, 14~
  85. Viardot A, "Phase 2 study of the bispecific T-cell engager(BiTE)antibody blinatumomab in relapsed", refractory diffuse large B-cell lymphoma, 2016, pp.127, 1410~1416
  86. Topp MS, "Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival", J Clin Oncol, 29, pp.2493~2498 (2011)
  87. Gökbuget N, "Long-term relapse-free survival in a phase 2 study of blinatumomab for the treatment of patients with minimal residual disease in B-lineage acute lymphoblastic leukemia", Haematologica, 102, pp.e132~e135 (2017)
  88. von Stackelberg A, "Phase I", phase II study of blinatumomab in pediatric patients with relapsed, J Clin Oncol, pp.2016, 34[DOI]
  89. Kantarjian H, "Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia", N Engl J Med, 376, pp.836~847 (2017)
  90. Topp MS, "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, 16, pp.57~66 (2015)
  91. Goebeler ME, "Bispecific T-cell engager(BiTE)antibody construct blinatumomab for the treatment of patients with relapsed", refractory non-Hodgkin lymphoma : final results from a phase I study, 2016, pp.34, 1104~1111
  92. Goebeler ME, "T cell-engaging therapies-BiTEs and beyond", Nat Rev Clin Oncol, 17, pp.418~434 (2020)
  93. Nagorsen D, "Immunotherapy of lymphoma and leukemia with T-cell engaging BiTE antibody blinatumomab", Leuk Lymphoma, 50, pp.886~891 (2009)
  94. Martinelli G, "Complete hematologic and molecular response in adult patients with relapsed", refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab : results from a phase II, single-arm, multicenter study, 2017, pp.35, 1795~1802
  95. Maude SL, "Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia", N Engl J Med, 378, pp.439~448 (2018)
  96. Lee DW, "T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults : a phase 1 dose-escalation trial", Lancet, 385, pp.517~528 (2015)
  97. Abramson JS, "Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas(TRANSCEND NHL 001) : a multicentre seamless design study", Lancet, 396, pp.839~852 (2020)
  98. Schuster SJ, "Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma", N Engl J Med, 380, pp.45~56 (2019)
  99. Neelapu SS, "Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma", N Engl J Med, 377, pp.2531~2544 (2017)
  100. Hoffmann P, "Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-", CD3-bispecific single-chain antibody construct, 2005, pp.115, 98~104
  101. Raponi S, "Flow cytometric study of potential target antigens(CD19, CD20, CD22, CD33)for antibody-based immunotherapy in acute lymphoblastic leukemia : analysis of 552 cases", Leuk Lymphoma, 52, pp.1098~1107 (2011)
  102. Dombret H, "Blinatumomab versus chemotherapy in first salvage or in later salvage for B-cell precursor acute lymphoblastic leukemia", Leuk Lymphoma, 60, pp.2214~2222 (2019)
  103. Berry DA, "Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia : a meta-analysis", JAMA Oncol, 3, pp.e170580~ (2017)
  104. Edeline J, "CAR-T cells and BiTEs in solid tumors : challenges and perspectives", J Hematol Oncol, 14, pp.65~ (2021)
  105. Kebenko M, "A multicenter phase 1 study of solitomab(MT110, AMG 110), a bispecific EpCAM", CD3 T-cell engager(BiTE®)antibody construct, in patients with refractory solid tumors, 2018, pp.7, e1450710~
  106. Yu WL, "Chimeric antigen receptor T-cell (CAR T) therapy for hematologic and solid malignancies: efficacy and safety-a systematic review with meta-analysis", Cancers(Basel), 11, pp.47~ (2019)
  107. Sebastian M, "Treatment of non-small cell lung cancer patients with the trifunctional monoclonal antibody catumaxomab(anti-EpCAM x anti-CD3) : a phase I study", Cancer Immunol Immunother, 56, pp.1637~1644 (2007)
  108. Heiss MM, "The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer : results of a prospective randomized phase II", III trial, 2010, pp.127, 2209~2221
  109. Borlak J, "Immune-mediated liver injury of the cancer therapeutic antibody catumaxomab targeting EpCAM, CD3 and Fcγ receptors", Oncotarget, 7, pp.28059~28074 (2016)
  110. Haense N, "A phase I trial of the trifunctional anti Her2 × anti CD3 antibody ertumaxomab in patients with advanced solid tumors", BMC Cancer, 16, pp.420~ (2016)
  111. Hummel HD, "Phase 1 study of pasotuxizumab (BAY 2010112), a PSMA-targeting bispecific T cell engager (BiTE) immunotherapy for metastatic castration-resistant prostate cancer (mCRPC)", J Clin Oncol, 37(15_suppl), pp.5034~ (2019)
  112. Asseman C, "An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation", J Exp Med, 190, pp.995~1004 (1999)
  113. Collison LW, "The inhibitory cytokine IL-35 contributes to regulatory T-cell function", Nature, 450, pp.566~569 (2007)
  114. Baratelli F, "Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells", J Immunol, 175, pp.1483~1490 (2005)
  115. Bronte V, "IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice", J Immunol, 170, pp.270~278 (2003)
  116. Youn JI, "Subsets of myeloid-derived suppressor cells in tumorbearing mice", J Immunol, 181, pp.5791~5802 (2008)
  117. Nagaraj S, "Antigen-specific CD4+ T cells regulate function of myeloid-derived suppressor cells in cancer via retrograde MHC class II signaling", Cancer Res, 72, pp.928~938 (2012)
  118. Lewis JS, "Expression of vascular endothelial growth factor by macrophages is up-regulated in poorly vascularized areas of breast carcinomas", J Pathol, 192, pp.150~158 (2000)
  119. Franklin RA, "The cellular and molecular origin of tumor-associated macrophages", Science, 344, pp.921~925 (2014)
  120. Cortez-Retamozo V, "Origins of tumor-associated macrophages and neutrophils", Proc Natl Acad Sci U S A, 109, pp.2491~2496 (2012)
  121. Trinklein ND, "Efficient tumor killing and minimal cytokine release with novel T-cell agonist bispecific antibodies", MAbs, 11, pp.639~652 (2019)
  122. Zuch de Zafra CL, "Targeting multiple myeloma with AMG 424, a novel anti-CD38", CD3 bispecific T-cell–recruiting antibody optimized for cytotoxicity and cytokine release, 2019, pp.25, 3921~3933
  123. Li J, "CD3 bispecific antibody-induced cytokine release is dispensable for cytotoxic T cell activity", Sci Transl Med, 11, pp.eaax8861~ (2019)
  124. Bortoletto N, "Optimizing anti-CD3 affinity for effective T cell targeting against tumor cells", Eur J Immunol, 32, pp.3102~3107 (2002)
  125. Bonvini E, "A next-generation Fc-bearing CD3-engaging bispecific dart® platform with extended pharmacokinetic and expanded pharmacologic window : characterization as CD123 X CD3 AND CD19 X CD3 dart molecules", Blood, 132, pp.5230~ (2018)
  126. Haber L, "Generation of T-cell-redirecting bispecific antibodies with differentiated profiles of cytokine release and biodistribution by CD3 affinity tuning", Sci Rep, 11, pp.14397~ (2021)
  127. Arvedson TL, "Abstract 55 : Generation of half-life extended anti-CD33 BiTE® antibody constructs compatible with once-weekly dosing", Cancer Res, 77, pp.55~ (2017)
  128. Lorenczewski G, "Generation of a half-life extended anti-CD19 BiTE® antibody construct compatible with once-weekly dosing for treatment of CD19-positive malignancies", Blood, 130, pp.2815~ (2017)
  129. Einsele H, "The BiTE(bispecific T-cell engager)platform : development and future potential of a targeted immuno-oncology therapy across tumor types", Cancer, 126, pp.3192~3201 (2020)

관련 논문AI추천

이중특이성 항체의 개발 및 최신동향한경호, Choi Yong Hwan, Kim Ji Hoe, Lee Su Keun, Song Chi Hun, Song Ha Seung한국미생물·생명공학회 · 한국미생물·생명공학회지2023 · 제51권 제3호Current Developments in NK Cell Engagers for Cancer Immunotherapy: Focus on CD16A and NKp46민도식, 신민화, Eunha Oh대한면역학회 · Immune Network2024 · 제24권 제5호Advances in T-Cell–Directed Immunotherapy for Adult Mature B-Cell Lymphoma: A Comprehensive Review of CAR T-Cell and Bispecific Antibody Therapies김석진, 김진철대한암학회 · Cancer Research and Treatment2025 · 제57권 제4호CAR T Cell Immunotherapy Beyond Haematological Malignancy김찬혁, 김효진, Hupperetz Cedric, Lah Sangjoon대한면역학회 · Immune Network2022 · 제22권 제1호The Past, Present, and Future of Adoptive T Cell Therapy김태규, 성영철, 최동훈대한면역학회 · Immune Network2012 · 제12권 제4호Bispecific antibodies and CLEM: an analytical approach to advanced cell imaging for therapeutic strategies김영관, 김한울한국현미경학회 · Applied Microscopy2025 · 제55권 제1호

이 간행물의 다른 논문 (12건)

Targeting the Epithelium-Derived Innate Cytokines: From Bench to Bedside김혜영, 신재우, 고병철, 함종호pp. 1-26Lessons From the Success and Failure of Targeted Drugs for Rheumatoid Arthritis: Perspectives for Effective Basic and Translational Research이상일, 김민교, 채용호pp. 1-20CAR T Cell Immunotherapy Beyond Haematological Malignancy김효진, 김찬혁, Hupperetz Cedric, Lah Sangjoonpp. 1-19Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy이병하, Wolfarth Alexandra A., Dhar Swati, Goon Jack B., Ezeanya Ugonna I., Ferrando-Martínez Sarapp. 1-22Targeted Immunotherapy for Autoimmune Disease김완욱, 정승민pp. 1-23
원문 보기