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Annual Review of Cancer Biology

Volume 6, 2022

Targeting Solid Tumors with Bispecific T Cell Engager Immune Therapy

Abstract

T cell engagers (TCEs) are targeted immunotherapies that have emerged as a promising treatment to redirect effector T cells for tumor cell killing. The strong therapeutic value of TCEs, established by the approval of blinatumomab for the treatment of B cell precursor acute lymphoblastic leukemia, has expanded to include other hematologic malignancies, as well as some solid tumors. Successful clinical development of TCEs in solid tumors has proven challenging, as it requires additional considerations such as the selectivity of target expression, tumor accessibility, and the impact of the immunosuppressive tumor microenvironment. In this review, we provide a brief history of blinatumomab, summarize learnings from TCEs in hematologic malignancies, and highlight results from recent TCE trials in solid tumors. Additionally, we examine approaches to improve the efficacy and safety of TCEs in solid tumors, including therapeutic combinations to increase the depth and durability of response.

Keyword(s): blinatumomab, combination therapy, cytokine release syndrome, solid tumors, T cell engager, tumor-associated antigen
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/content/journals/10.1146/annurev-cancerbio-070620-104325
2022-04-11
2024-04-19
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Literature Cited

  1. Aldoss I, Uy GL, Vey N, Emadi A, Sayre PH et al. 2020. Flotetuzumab as salvage therapy for primary induction failure and early relapse acute myeloid leukemia. Blood 136:Suppl. 116–18
     [Google Scholar]
  2. Argilés G, Saro J, Segal NH, Melero I, Ros W et al. 2017. Novel carcinoembryonic antigen T-cell bispecific (CEA-TCB) antibody: preliminary clinical data as a single agent and in combination with atezolizumab in patients with metastatic colorectal cancer (mCRC). Ann. Oncol. 28:Suppl. 3III151 (Abstr.)
     [Google Scholar]
  3. Bannerji R, Allan JN, Arnason JE, Brown JR, Advani R et al. 2020. Odronextamab (REGN1979), a human CD20 × CD3 bispecific antibody, induces durable, complete responses in patients with highly refractory B-cell non-Hodgkin lymphoma, including patients refractory to CAR T therapy. Blood 136:Suppl. 142–43
     [Google Scholar]
  4. Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M et al. 2008. Tumor regression in cancer patients by very low doses of a T cell–engaging antibody. Science 321:974–77
     [Google Scholar]
  5. Belmontes B, Sawant DV, Zhong W, Tan H, Kaul A et al. 2021. Immunotherapy combinations overcome resistance to bispecific T cell engager treatment in T cell–cold solid tumors. Sci Transl Med. 13:608eabd1524
     [Google Scholar]
  6. Bendell JC, Fong L, Stein MN, Beer TM, Ross A et al. 2020. First-in-human phase I study of HPN424, a tri-specific half-life extended PSMA-targeting T-cell engager in patients with metastatic castration-resistant prostate cancer (mCRPC). J. Clin. Oncol. 38:5552
     [Google Scholar]
  7. Benonisson H, Altıntaş I, Sluijter M, Verploegen S, Labrijn AF et al. 2019. CD3-bispecific antibody therapy turns solid tumors into inflammatory sites but does not install protective memory. Mol. Cancer Ther. 18:312–22
     [Google Scholar]
  8. Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF et al. 2018. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 24:541–50
     [Google Scholar]
  9. Blinatumomab [package insert] 2018. Thousand Oaks, CA: Amgen Inc.
  10. Borghaei H, Boyer M, Johnson M, Govindan R, Rodrigues LP-A et al. 2020. AMG 757, a half-life extended bispecific T-cell engager (BiTE®) immune therapy against DLL3 in SCLC: phase 1 interim results Abstract presented at the Society for Immunotherapy of Cancer Virtual: Nov. 9–14
  11. Boustany LM, Wong L, White CW, Diep L, Huang Y et al. 2018. EGFR-CD3 bispecific Probody™ therapeutic induces tumor regressions and increases maximum tolerated dose >60-fold in preclinical studies. Mol. Cancer Ther. 17:Suppl. 1A164 (Abstr.)
     [Google Scholar]
  12. Brischwein K, Parr L, Pflanz S, Volkland J, Lumsden J et al. 2007. Strictly target cell-dependent activation of T cells by bispecific single-chain antibody constructs of the BiTE class. J. Immunother. 30:798–807
     [Google Scholar]
  13. Bruni D, Angell HK, Galon J. 2020. The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy. Nat. Rev. Cancer 20:662–80
     [Google Scholar]
  14. Burges A, Wimberger P, Kümper C, Gorbounova V, Sommer H et al. 2007. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM × anti-CD3 antibody: a phase I/II study. Clin. Cancer Res. 13:3899–905
     [Google Scholar]
  15. Cattaruzza F, Nazeer A, Lange Z, Koski C, Hammond M et al. 2020. HER2-XPAT, a novel protease-activatable prodrug T cell engager (TCE), with potent T-cell activation and efficacy in solid tumors and large predicted safety margins in non-human primate (NHP). J. Immunother. Cancer 8:A368–69
     [Google Scholar]
  16. Chari A, Berdeja JG, Oriol A, van de Donk NWCJ, Rodriguez P et al. 2020. A phase 1, first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D (GPRC5D) × CD3 bispecific antibody, in patients with relapsed and/or refractory multiple myeloma (RRMM). Blood 136:Suppl. 140–41
     [Google Scholar]
  17. Choi BD, Gedeon PC, Herndon JE2nd, Archer GE, Reap EA et al. 2013. Human regulatory T cells kill tumor cells through granzyme-dependent cytotoxicity upon retargeting with a bispecific antibody. Cancer Immunol. Res. 1:163
     [Google Scholar]
  18. Cohen AD, Harrison SJ, Krishnan A, Fonseca R, Forsberg PA et al. 2020. Initial clinical activity and safety of BFCR4350A, a FcRH5/CD3 T-cell-engaging bispecific antibody, in relapsed/refractory multiple myeloma. Blood 136:Suppl. 142–43
     [Google Scholar]
  19. Correnti CE, Laszlo GS, de van der Schueren WJ, Godwin CD, Bandaranayake A et al. 2018. Simultaneous multiple interaction T-cell engaging (SMITE) bispecific antibodies overcome bispecific T-cell engager (BiTE) resistance via CD28 co-stimulation. Leukemia 32:1239–43
     [Google Scholar]
  20. Costa LJ, Wong SW, Bermúdez A, de la Rubia J, Mateos M-V et al. 2019. First clinical study of the B-cell maturation antigen (BCMA) 2+1 T cell engager (TCE) CC-93269 in patients (pts) with relapsed/refractory multiple myeloma (RRMM): interim results of a phase 1 multicenter trial. Blood 134:Suppl. 1143
     [Google Scholar]
  21. Coyle L, Morley NJ, Rambaldi A, Mason KD, Verhoef G et al. 2018. Open-label, phase 2 study of blinatumomab as second salvage therapy in adults with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Blood 132:Suppl. 1400
     [Google Scholar]
  22. d'Argouges S, Wissing S, Brandl C, Prang N, Lutterbuese R et al. 2009. Combination of rituximab with blinatumomab (MT103/MEDI-538), a T cell-engaging CD19-/CD3-bispecific antibody, for highly efficient lysis of human B lymphoma cells. Leuk. Res. 33:465–73
     [Google Scholar]
  23. Deshaies RJ. 2020. Multispecific drugs herald a new era of biopharmaceutical innovation. Nature 580:329–38
     [Google Scholar]
  24. Desnoyers LR, Vasiljeva O, Richardson JH, Yang A, Menendez EE et al. 2013. Tumor-specific activation of an EGFR-targeting probody enhances therapeutic index. Sci. Transl. Med. 5:207ra144
     [Google Scholar]
  25. Dettling D, Kwok E, Quach L, Datt A, Degenhardt JD et al. 2019. COBRA: a novel conditionally active bispecific antibody that regresses established solid tumors in mice. Cancer Res 79:Suppl. 13557 (Abstr.)
     [Google Scholar]
  26. Dickinson MJ, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC et al. 2020. CD20-TCB in relapsed or refractory non-Hodgkin lymphoma: durable complete responses and manageable safety observed at clinically relevant doses in phase I dose escalation Abstract presented at the 25th European Hematology Association Annual Congress Virtual: June 11–21
  27. Duell J, Dittrich M, Bedke T, Mueller T, Eisele F et al. 2017. Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL. Leukemia 31:2181–90
     [Google Scholar]
  28. Dufner V, Sayehli CM, Chatterjee M, Hummel HD, Gelbrich G et al. 2019. Long-term outcome of patients with relapsed/refractory B-cell non-Hodgkin lymphoma treated with blinatumomab. Blood Adv. 3:2491–98
     [Google Scholar]
  29. El-Rayes B, Pant S, Villalobos V, Hendifar A, Chow W et al. 2020. Preliminary safety, PK/PD, and antitumor activity of XmAb18087, an SSTR2 × CD3 bispecific antibody, in patients with advanced neuroendocrine tumors Abstract presented at The North American Neuroendocrine Tumor Society, Virtual: Oct. 1–3
  30. Feucht J, Kayser S, Gorodezki D, Hamieh M, Döring M et al. 2016. T-cell responses against CD19+ pediatric acute lymphoblastic leukemia mediated by bispecific T-cell engager (BiTE) are regulated contrarily by PD-L1 and CD80/CD86 on leukemic blasts. Oncotarget 7:76902–19
     [Google Scholar]
  31. Garfall AL, Usmani SZ, Mateos M-V, Nahi H, van de Donk NWCJ et al. 2020. Updated phase 1 results of teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, in relapsed and/or refractory multiple myeloma (RRMM). Blood 136:Suppl. 127
     [Google Scholar]
  32. Giffin MJ, Cooke K, Lobenhofer EK, Estrada J, Zhan J et al. 2021. AMG 757, a half-life extended, DLL3-targeted bispecific T-cell engager, shows high potency and sensitivity in preclinical models of small-cell lung cancer. Clin. Cancer Res. 27:1526–37
     [Google Scholar]
  33. Goebeler ME, Bargou RC. 2020. T cell-engaging therapies—BiTEs and beyond. Nat. Rev. Clin. Oncol. 17:418–34
     [Google Scholar]
  34. Gökbuget N, Dombret H, Bonifacio M, Reichle A, Graux C et al. 2018. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood 131:1522–31
     [Google Scholar]
  35. Griessinger CM, Olafsen T, Mascioni A, Jiang ZK, Zamilpa C et al. 2020. The PET-Tracer 89Zr-Df-IAB22M2C enables monitoring of intratumoral CD8 T-cell infiltrates in tumor-bearing humanized mice after T-cell bispecific antibody treatment. Cancer Res 80:2903–13
     [Google Scholar]
  36. Haas C, Krinner E, Brischwein K, Hoffmann P, Lutterbüse R et al. 2009. Mode of cytotoxic action of T cell-engaging BiTE antibody MT110. Immunobiology 214:441–53
     [Google Scholar]
  37. Harrison SJ, Minnema MC, Lee HC, Spencer A, Kapoor P et al. 2020. A phase 1 first in human (FIH) study of AMG 701, an anti-B-cell maturation antigen (BCMA) half-life extended (HLE) BiTE® (bispecific T-cell engager) molecule, in relapsed/refractory (RR) multiple myeloma (MM). Blood 136:Suppl. 128–29
     [Google Scholar]
  38. Heiss MM, Murawa P, Koralewski P, Kutarska E, Kolesnik OO et al. 2010. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int. J. Cancer 127:2209–21
     [Google Scholar]
  39. Helftenbein G, Koslowski M, Dhaene K, Seitz G, Sahin U, Türeci Ö. 2008. In silico strategy for detection of target candidates for antibody therapy of solid tumors. Gene 414:76–84
     [Google Scholar]
  40. Hijazi Y, Klinger M, Kratzer A, Wu B, Baeuerle PA et al. 2018. Pharmacokinetic and pharmacodynamic relationship of blinatumomab in patients with non-Hodgkin lymphoma. Curr. Clin. Pharmacol. 13:55–64
     [Google Scholar]
  41. Ho WJ, Jaffee EM, Zheng L. 2020. The tumour microenvironment in pancreatic cancer—clinical challenges and opportunities. Nat. Rev. Clin. Oncol. 17:527–40
     [Google Scholar]
  42. Hoffmann P, Hofmeister R, Brischwein K, Brandl C, Crommer S et al. 2005. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/CD3-bispecific single-chain antibody construct. Int. J. Cancer 115:98–104
     [Google Scholar]
  43. Hosseini I, Gadkar K, Stefanich E, Li CC, Sun LL et al. 2020. Mitigating the risk of cytokine release syndrome in a phase I trial of CD20/CD3 bispecific antibody mosunetuzumab in NHL: impact of translational system modeling. NPJ Syst. Biol. Appl. 6:28
     [Google Scholar]
  44. Hummel HD, Kufer P, Grüllich C, Seggewiss-Bernhardt R, Deschler-Baier B et al. 2021. Pasotuxizumab, a BiTE® immune therapy for castration-resistant prostate cancer: phase I, dose-escalation study findings. Immunotherapy 13:125–41
     [Google Scholar]
  45. Hutchings M, Lugtenburg P, Mous R, Clausen MR, Chamuleau M et al. 2020. Epcoritamab (GEN3013; DuoBody-CD3×CD20) to induce complete response in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL): complete dose escalation data and efficacy results from a phase I/II trial. J. Clin. Oncol. 38:8009
     [Google Scholar]
  46. Hutchings M, Morschhauser F, Iacoboni G, Carlo-Stella C, Offner FC et al. 2021. Glofitamab, a novel, bivalent CD20-targeting T-cell-engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: a phase I trial. J. Clin. Oncol. 39:181959–70
     [Google Scholar]
  47. Ishiguro T, Sano Y, Komatsu SI, Kamata-Sakurai M, Kaneko A et al. 2017. An anti-glypican 3/CD3 bispecific T cell-redirecting antibody for treatment of solid tumors. Sci. Transl. Med. 9:eaal4291
     [Google Scholar]
  48. June CH, O'Connor RS, Kawalekar OU, Ghassemi S, Milone MC 2018. CAR T cell immunotherapy for human cancer. Science 359:1361–65
     [Google Scholar]
  49. Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC et al. 2017. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N. Engl. J. Med. 376:836–47
     [Google Scholar]
  50. Kebenko M, Goebeler ME, Wolf M, Hasenburg A, Seggewiss-Bernhardt R et al. 2018. 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. OncoImmunology 7:e1450710
     [Google Scholar]
  51. Kim KH, Cho J, Ku BM, Koh J, Sun J-M et al. 2019. The first-week proliferative response of peripheral blood PD-1+ CD8+ T cells predicts the response to anti-PD-1 therapy in solid tumors. Clin. Cancer Res. 25:2144–54
     [Google Scholar]
  52. Klinger M, Brandl C, Zugmaier G, Hijazi Y, Bargou RC et al. 2012. Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE antibody blinatumomab. Blood 119:6226–33
     [Google Scholar]
  53. Klinger M, Zugmaier G, Nägele V, Goebeler ME, Brandl C et al. 2020. Adhesion of T cells to endothelial cells facilitates blinatumomab-associated neurologic adverse events. Cancer Res 80:91–101
     [Google Scholar]
  54. Krupka C, Kufer P, Kischel R, Zugmaier G, Lichtenegger FS et al. 2016. Blockade of the PD-1/PD-L1 axis augments lysis of AML cells by the CD33/CD3 BiTE antibody construct AMG 330: reversing a T-cell-induced immune escape mechanism. Leukemia 30:484–91
     [Google Scholar]
  55. Lajoie MJ, Boyken SE, Salter AI, Bruffey J, Rajan A et al. 2020. Designed protein logic to target cells with precise combinations of surface antigens. Science 369:1637–43
     [Google Scholar]
  56. Laszlo GS, Gudgeon CJ, Harrington KH, Walter RB. 2015. T-cell ligands modulate the cytolytic activity of the CD33/CD3 BiTE antibody construct, AMG 330. Blood Cancer J 5:e340
     [Google Scholar]
  57. Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N et al. 2014. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124:188–95
     [Google Scholar]
  58. Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ et al. 2019. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol. Blood Marrow Transplant. 25:625–38
     [Google Scholar]
  59. Leong SR, Sukumaran S, Hristopoulos M, Totpal K, Stainton S et al. 2017. An anti-CD3/anti-CLL-1 bispecific antibody for the treatment of acute myeloid leukemia. Blood 129:609–18
     [Google Scholar]
  60. Lesokhin A, Levy M, Dalovisio AP, Bahlis N, Solh M et al. 2020. Preliminary safety, efficacy, pharmacokinetics, and pharmacodynamics of subcutaneously (SC) administered PF-06863135, a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). Blood 136:Suppl. 18–9
     [Google Scholar]
  61. Li J, Piskol R, Ybarra R, Chen YJ, Li J et al. 2019. CD3 bispecific antibody–induced cytokine release is dispensable for cytotoxic T cell activity. Sci. Transl. Med. 11:eaax8861
     [Google Scholar]
  62. Li J, Ybarra R, Mak J, Herault A, De Almeida P et al. 2018. IFNγ-induced chemokines are required for CXCR3-mediated T-cell recruitment and antitumor efficacy of anti-HER2/CD3 bispecific antibody. Clin. Cancer Res. 24:6447–58
     [Google Scholar]
  63. Lim AR, Rathmell WK, Rathmell JC. 2020. The tumor microenvironment as a metabolic barrier to effector T cells and immunotherapy. eLife 9:e55185
     [Google Scholar]
  64. Lin J, Rocha S, Kwant K, Dayao M, Ng T et al. 2020. HPN601 is a protease-activated EpCAM-targeting T cell engager with an improved safety profile for the treatment of solid tumors. J. Immunother. Cancer 8:Suppl. 3A379
     [Google Scholar]
  65. Linke R, Klein A, Seimetz D. 2010. Catumaxomab: clinical development and future directions. mAbs 2:129–36
     [Google Scholar]
  66. Löffler A, Kufer P, Lutterbüse R, Zettl F, Daniel PT et al. 2000. A recombinant bispecific single-chain antibody, CD19 × CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood 95:2098–103
     [Google Scholar]
  67. Madduri D, Rosko A, Brayer J, Zonder J, Bensinger WI et al. 2020. REGN5458, a BCMA × CD3 bispecific monoclonal antibody, induces deep and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). Blood 136:Suppl. 141–42
     [Google Scholar]
  68. Malik-Chaudhry HK, Prabhakar K, Ugamraj HS, Boudreau AA, Buelow B et al. 2021. TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL. mAbs 13:1890411
     [Google Scholar]
  69. Matasar M, Cheah C, Yoon D, Assouline S, Bartlett N et al. 2020. Subcutaneous mosunetuzumab in relapsed or refractory B-cell lymphoma: promising safety and encouraging efficacy in dose escalation cohorts. Blood 136:Suppl. 145–46
     [Google Scholar]
  70. Middleton MR, McAlpine C, Woodcock VK, Corrie P, Infante JR et al. 2020. Tebentafusp, a TCR/anti-CD3 bispecific fusion protein targeting gp100, potently activated antitumor immune responses in patients with metastatic melanoma. Clin. Cancer Res. 26:5869–78
     [Google Scholar]
  71. Moek KL, Fiedler WM, von Einem JC, Verheul HM, Seufferlein T et al. 2018. Phase I study of AMG 211/MEDI-565 administered as continuous intravenous infusion (cIV) for relapsed/refractory gastrointestinal (GI) adenocarcinoma. Ann. Oncol. 29:viii139–40
     [Google Scholar]
  72. Moore PA, Shah K, Yang Y, Alderson R, Roberts P et al. 2018. Development of MGD007, a gpA33 × CD3-bispecific DART protein for T-cell immunotherapy of metastatic colorectal cancer. Mol. Cancer Ther. 17:1761–72
     [Google Scholar]
  73. Nägele V, Kratzer A, Zugmaier G, Holland C, Hijazi Y et al. 2017. Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL. Exp. Hematol. Oncol. 6:14
     [Google Scholar]
  74. Nagorsen D, Kufer P, Baeuerle PA, Bargou R. 2012. Blinatumomab: a historical perspective. Pharmacol. Ther. 136:334–42
     [Google Scholar]
  75. Nolan-Stevaux O. 2020. AMG 509: a novel, humanized, half-life extended, bispecific STEAP1 × CD3 T cell recruiting XmAb® 2+1 antibody. Cancer Res 80:Suppl. 16DDT02-03 (Abstr.)
     [Google Scholar]
  76. Offner S, Hofmeister R, Romaniuk A, Kufer P, Baeuerle PA. 2006. Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells. Mol. Immunol. 43:763–71
     [Google Scholar]
  77. Olszewski AJ, Avigdor A, Babu S, Levi I, Abadi U et al. 2020. Single-agent mosunetuzumab is a promising safe and efficacious chemotherapy-free regimen for elderly/unfit patients with previously untreated diffuse large B-cell lymphoma. Blood 136:Suppl. 143–45
     [Google Scholar]
  78. Owonikoko TK, Champiat S, Johnson ML, Govindan R, Izumi H et al. 2021. Updated results from a phase 1 study of AMG 757, a half-life extended bispecific T-cell engager (BiTE) immuno-oncology therapy against delta-like ligand 3 (DLL3), in small cell lung cancer (SCLC) Poster presented at 2021 ASCO Annual Meeting Online: June 4–8
  79. Parker KR, Migliorini D, Perkey E, Yost KE, Bhaduri A et al. 2020. Single-cell analyses identify brain mural cells expressing CD19 as potential off-tumor targets for CAR-T immunotherapies. Cell 183:126–42.e17
     [Google Scholar]
  80. Ravandi F, Bashey A, Stock W, Foran JM, Mawad R et al. 2020a. Complete responses in relapsed/refractory acute myeloid leukemia (AML) patients on a weekly dosing schedule of vibecotamab (XmAb14045), a CD123 × CD3 T cell-engaging bispecific antibody; initial results of a phase 1 study. Blood 136:Suppl. 14–5
     [Google Scholar]
  81. Ravandi F, Walter RB, Subklewe M, Buecklein V, Jongen-Lavrencic M et al. 2020b. Updated results from phase I dose-escalation study of AMG 330, a bispecific T-cell engager molecule, in patients with relapsed/refractory acute myeloid leukemia (R/R AML). J. Clin. Oncol. 38:Suppl. 157508
     [Google Scholar]
  82. Rius Ruiz I, Vicario R, Morancho B, Morales CB, Arenas EJ et al. 2018. p95HER2-T cell bispecific antibody for breast cancer treatment. Sci. Transl. Med. 10:eaat1445
     [Google Scholar]
  83. Rodriguez C, D'Souza A, Shah N, Voorhees PM, Buelow B et al. 2020. Initial results of a phase I study of TNB-383B, a BCMA × CD3 bispecific T-cell redirecting antibody, in relapsed/refractory multiple myeloma. Blood 136:Suppl. 143–44
     [Google Scholar]
  84. Sacco JJ, Carvajal R, Butler M, Shoushtari A, Hassel J et al. 2020. A phase (ph) II, multi-center study of the safety and efficacy of tebentafusp (tebe) (IMCgp100) in patients (pts) with metastatic uveal melanoma (mUM). Ann. Oncol. 31:Suppl. 7S1441–51
     [Google Scholar]
  85. Saunders LR, Bankovich AJ, Anderson WC, Aujay MA, Bheddah S et al. 2015. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci. Transl. Med. 7:302ra136
     [Google Scholar]
  86. Sawant D, Belmontes B, Aeffner F, Nolan-Stevaux O, Egen J, DeVoss J 2019. Informing rational immunotherapy combinations for enhancing therapeutic activity of bi-specific T cell engager (BiTE®) antibody constructs in solid tumors. J. Immunother. Cancer 7:283
     [Google Scholar]
  87. Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA et al. 2018. Cytokine release syndrome. J. Immunother. Cancer 6:56
     [Google Scholar]
  88. Spranger S, Gajewski TF. 2018. Mechanisms of tumor cell–intrinsic immune evasion. Annu. Rev. Cancer Biol. 2:213–28
     [Google Scholar]
  89. Subklewe M. 2021. BiTEs better than CAR T cells. Blood Adv. 5:607–12
     [Google Scholar]
  90. Subklewe M, Stein A, Walter RB, Bhatia R, Wei AH et al. 2019. Preliminary results from a phase 1 first-in-human study of AMG 673, a novel half-life extended (HLE) anti-CD33/CD3 BiTE® (bispecific T-cell engager) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). Blood 134:Suppl. 1833
     [Google Scholar]
  91. Sun R, Limkin EJ, Vakalopoulou M, Dercle L, Champiat S et al. 2018. A radiomics approach to assess tumour-infiltrating CD8 cells and response to anti-PD-1 or anti-PD-L1 immunotherapy: an imaging biomarker, retrospective multicohort study. Lancet Oncol. 19:1180–91
     [Google Scholar]
  92. Tabernero J, Melero I, Ros W, Argiles G, Marabelle A et al. 2017. Phase Ia and Ib studies of the novel carcinoembryonic antigen (CEA) T-cell bispecific (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab: preliminary efficacy and safety in patients with metastatic colorectal cancer (mCRC). J. Clin. Oncol. 35:Suppl. 153002
     [Google Scholar]
  93. Topp MS, Duell J, Zugmaier G, Attal M, Moreau P et al. 2020. Anti-B-cell maturation antigen BiTE molecule AMG 420 induces responses in multiple myeloma. J. Clin. Oncol. 38:775–83
     [Google Scholar]
  94. Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S et al. 2015. 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. 16:57–66
     [Google Scholar]
  95. Topp MS, Gökbuget N, Zugmaier G, Klappers P, Stelljes M et al. 2014. 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. 32:4134–40
     [Google Scholar]
  96. Tran B, Horvath L, Dorff T, Rettig M, Lolkema MP et al. 2020. 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) Abstract presented at European Society for Medical Oncology Congress 2020 Virtual: Sep. 19–21
  97. Trinklein ND, Pham D, Schellenberger U, Buelow B, Boudreau A et al. 2019. Efficient tumor killing and minimal cytokine release with novel T-cell agonist bispecific antibodies. mAbs 11:639–52
     [Google Scholar]
  98. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ et al. 2014. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515:568–71
     [Google Scholar]
  99. Uryvaev A, Passhak M, Hershkovits D, Sabo E, Bar-Sela G. 2018. The role of tumor-infiltrating lymphocytes (TILs) as a predictive biomarker of response to anti-PD1 therapy in patients with metastatic non-small cell lung cancer or metastatic melanoma. Med. Oncol. 35:25
     [Google Scholar]
  100. Wei SC, Duffy CR, Allison JP. 2018. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov 8:1069–86
     [Google Scholar]
  101. Wu Z, Cheung NV. 2018. T cell engaging bispecific antibody (T-BsAb): from technology to therapeutics. Pharmacol. Ther. 182:161–75
     [Google Scholar]
  102. Zuch de Zafra CL, Fajardo F, Zhong W, Bernett MJ, Muchhal US et al. 2019. Targeting multiple myeloma with AMG 424, a novel anti-CD38/CD3 bispecific T-cell-recruiting antibody optimized for cytotoxicity and cytokine release. Clin. Cancer Res. 25:3921–33
     [Google Scholar]
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Targeting Solid Tumors with Bispecific T Cell Engager Immune Therapy
Annual Review of Cancer Biology 6, 17 (2022); https://doi.org/10.1146/annurev-cancerbio-070620-104325
/content/journals/10.1146/annurev-cancerbio-070620-104325
/content/journals/10.1146/annurev-cancerbio-070620-104325
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