CEA/CD3-bispecific T cell-engaging (BiTE) antibody-mediated T lymphocyte cytotoxicity maximized by inhibition of both PD1 and PD-L1

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• 作者：Takuya Osada ; Sandip P. Patel ; Scott A. Hammond…
• 关键词：PD ; 1 ; PD ; L1 ; T cell cytotoxicity ; CEA BiTE ; Immunotherapy
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：64
• 期：6
• 页码：677-688
• 全文大小：1,928 KB
• 参考文献：1.Pag猫s F, Berger A, Camus M et al (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353:2654鈥?666PubMed View Article
  2.Nomi T, Sho M, Akahori T et al (2007) Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res 13:2151鈥?157PubMed View Article
  3.Mosolits S, Ullenhag G, Mellstedt H (2005) Therapeutic vaccination in patients with gastrointestinal malignancies. A review of immunological and clinical results. Ann Oncol 16:847鈥?62PubMed View Article
  4.Karlsson M, Marits P, Dahl K et al (2010) Pilot study of sentinel-node-based adoptive immunotherapy in advanced colorectal cancer. Ann Surg Oncol 17:1747鈥?757PubMed Central PubMed View Article
  5.Kobari M, Egawa S, Shibuya K, Sunamura M, Saitoh K, Matsuno S (2000) Effect of intraportal adoptive immunotherapy on liver metastases after resection of pancreatic cancer. Br J Surg 87:43鈥?8PubMed View Article
  6.Dudley ME, Wunderlich JR, Shelton TE, Even J, Rosenberg SA (2003) Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunother 26:332PubMed Central PubMed View Article
  7.Bargou R, Leo E, Zugmaier G et al (2008) Tumor regression in cancer patients by very low doses of a t cell-engaging antibody. Science 321:974鈥?77PubMed View Article
  8.Klinger M, Brandl C, Zugmaier G 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鈥?233PubMed View Article
  9.Hammarstrom S (1999) The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol 9:67鈥?1PubMed View Article
  10.Lutterbuese R, Raum T, Kischel R, Lutterbuese P, Schlereth B, Schaller E, Mangold S, Rau D, Meier P, Kiener PA, Mulgrew K, Oberst MD, Hammond SA, Baeuerle PA, Kufer P (2009) Potent control of tumor growth by CEA/CD3-bispecific single-chain antibody constructs that are not competitively inhibited by soluble CEA. J Immunother 32:341鈥?52PubMed View Article
  11.Lutterbuese R, Raum T, Kischel R et al (2009) Potent control of tumor growth by CEA/CD3-bispecific single-chain antibody constructs that are not competitively inhibited by soluble CEA. J Immunother 32:341PubMed View Article
  12.Osada T, Hsu D, Hammond S et al (2009) Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitive to T-cell killing mediated by CEA/CD3-bispecific T-cell-engaging BiTE antibody. Br J Cancer 102:124鈥?33PubMed Central PubMed View Article
  13.Khong HT, Restifo NP (2002) Natural selection of tumor variants in the generation of 鈥渢umor escape鈥?phenotypes. Nat Immunol 3:999鈥?005PubMed Central PubMed View Article
  14.Derynck R, Akhurst RJ, Balmain A (2001) TGF-[beta] signaling in tumor suppression and cancer progression. Nat Genet 29:117鈥?29PubMed View Article
  15.Ferrone S, Whiteside TL (2007) Tumor microenvironment and immune escape. Surg Oncol Clin N Am 16:755鈥?74PubMed View Article
  16.Nagaraj S, Gabrilovich DI (2008) Tumor escape mechanism governed by myeloid-derived suppressor cells. Cancer Res 68:2561鈥?563PubMed View Article
  17.Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ (2007) The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol 8:239鈥?45PubMed View Article
  18.Freeman GJ, Long AJ, Iwai Y et al (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027鈥?034PubMed Central PubMed View Article
  19.Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC (2010) Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med 207:2187鈥?194PubMed Central PubMed View Article
  20.Ribas A (2012) Tumor immunotherapy directed at PD-1. N Engl J Med 366(26):2517鈥?519PubMed View Article
  21.Brischwein K, Schlereth B, Guller B et al (2006) MT110: a novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors. Mol Immunol 43:1129鈥?143PubMed View Article
  22.Baeuerle PA, Reinhardt C (2009) Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res 69:4941鈥?944PubMed View Article
  23.Lee SJ, Jang BC, Lee SW, Yang YI, Suh SI, Park YM, Oh S, Shin JG, Yao S, Chen L, Choi IH (2006) Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). FEBS Lett 580(3):755鈥?62PubMed View Article
  24.Brischwein K, Parr L, Pflanz S et al (2007) Strictly target cell-dependent activation of T cells by bispecific single-chain antibody constructs of the BiTE class. J Immunother 30(8):798鈥?07PubMed View Article
  25.Mathieu M, Cotta-Grand N, Daudelin JF, Th茅bault P, Labrecque N (2013) Notch signaling regulates PD-1 expression during CD8(+) T-cell activation. Immunol Cell Biol 91(1):82鈥?8PubMed View Article
  26.Curran MA, Montalvo W, Yagita H, Allison JP (2010) PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci USA 107:4275鈥?280PubMed Central PubMed View Article
  27.Keir ME, Francisco LM, Sharpe AH (2007) PD-1 and its ligands in T-cell immunity. Curr Opin Immunol 19:309鈥?14PubMed View Article
  28.Dong H, Strome SE, Salomao DR et al (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793鈥?00PubMed
  29.Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N (2002) Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA 99(19):12293鈥?2297PubMed Central PubMed View Article
  30.Ha SJ, Mueller SN, Wherry EJ et al (2008) Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection. J Exp Med 205(3):543鈥?55PubMed Central PubMed View Article
  31.Wu X, Zhang H, Xing Q, Cui J, Li J, Li Y, Tan Y, Wang S (2014) PD-1(+) CD8(+) T cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients. Br J Cancer 111(7):1391鈥?399PubMed View Article
  32.Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12(4):252鈥?64PubMed View Article
  33.Ghiotto M, Gauthier L, Serriari N, Pastor S, Truneh A, Nun猫s JA, Olive D (2010) PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1. Int Immunol 22(8):651鈥?60PubMed Central PubMed View Article
  34.Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ (2007) Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 27:111鈥?22PubMed Central PubMed View Article
  35.Topp MS, G枚kbuget N, Zugmaier G et al (2012) Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood 120:5185鈥?187PubMed View Article
  36.Hodi FS, O鈥橠ay SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711鈥?23PubMed Central PubMed View Article
  37.Topalian SL, Hodi FS, Brahmer JR et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443鈥?454PubMed Central PubMed View Article
  38.Brahmer JR, Tykodi SS, Chow LQM et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455鈥?465PubMed Central PubMed View Article
  
• 作者单位：Takuya Osada (1) (3) (5)
  Sandip P. Patel (2) (6)
  Scott A. Hammond (4)
  Koya Osada (1)
  Michael A. Morse (2) (3)
  H. Kim Lyerly (1) (3)
  
  1. Section of Applied Therapeutics, Department of Surgery, Duke University Medical Center, 403 MSRB, Research Drive, Durham, NC, 27710, USA
  3. Duke Comprehensive Cancer Center, Duke University Medical Center, 403 MSRB, Research Drive, Durham, NC, 27710, USA
  5. 443A MSRB 1, Research DR, Durham, NC, 27710, USA
  2. Department of Medicine, Duke University Medical Center, 403 MSRB, Research Drive, Durham, NC, 27710, USA
  6. University of California (UC) San Diego Moores Cancer Center, La Jolla, CA, USA
  4. MedImmune LLC, One MedImmune Way, Gaithersburg, MD, 20878, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Immunology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0851

文摘

Bispecific T cell-engaging (BiTE) antibodies recruit polyclonal cytotoxic T cells (CTL) to tumors. One such antibody is carcinoembryonic antigen (CEA) BiTE that mediates T cell/tumor interaction by simultaneously binding CD3 expressed by T cells and CEA expressed by tumor cells. A widely operative mechanism for mitigating cytotoxic T cell-mediated killing is the interaction of tumor-expressed PD-L1 with T cell-expressed PD-1, which may be partly reversed by PD-1/PD-L1 blockade. We hypothesized that PD-1/PD-L1 blockade during BiTE-mediated T cell killing would enhance CTL function. Here, we determined the effects of PD-1 and PD-L1 blockade during initial T cell-mediated killing of CEA-expressing human tumor cell lines in vitro, as well as subsequent T cell-mediated killing by T lymphocytes that had participated in tumor cell killing. We observed a rapid upregulation of PD-1 expression and diminished cytolytic function of T cells after they had engaged in CEA BiTE-mediated killing of tumors. T cell cytolytic activity in vitro could be maximized by administration of anti-PD-1 or anti-PD-L1 antibodies alone or in combination if applied prior to a round of T cell killing, but T cell inhibition could not be fully reversed by this blockade once the T cells had killed tumor. In conclusion, our findings demonstrate that dual blockade of PD-1 and PD-L1 maximizes T cell killing of tumor directed by CEA BiTE in vitro, is more effective if applied early, and provides a rationale for clinical use.