The Tumor Targeted Superantigen ABR-217620 Selectively Engages TRBV7-9 and Exploits TCR-pMHC Affinity Mimicry in Mediating T Cell Cytotoxicity

PLoS ONE

Volumn 8, Issue 10, 2013, Pages

  Hedlund, Gunnar ^a   Eriksson, Helena ^a   Sundstedt, Anette ^a   Forsberg, Göran ^a   Jakobsen, Bent K ^b   Pumphrey, Nicholas ^c   Rödström, Karin ^d   Lindkvist Petersson, Karin ^d   Björk, Per ^a  

^a Active Biotech Research AB   (Sweden)

^b Immunocore Limited   (United Kingdom)

^c Adaptimmune Ltd   (United Kingdom)

^d LUND UNIVERSITY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

HYBRID PROTEIN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; NAPTUMOMAB ESTAFENATOX; PROTEIN 5T4; PROTEIN TRBV7 9; SUPERANTIGEN; T LYMPHOCYTE RECEPTOR BETA CHAIN; TOLL LIKE RECEPTOR; TUMOR ANTIGEN; UNCLASSIFIED DRUG; ANTIBODY CONJUGATE; ANTINEOPLASTIC AGENT; ENTEROTOXIN; ENTEROTOXIN A E-120, STAPHYLOCOCCAL; LUCIFERASE; MEMBRANE PROTEIN; MONOCLONAL ANTIBODY; PRIMER DNA; TROPHOBLASTIC GLYCOPROTEIN 5T4, HUMAN;

ANTIGEN SPECIFICITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING AFFINITY; CELL EXPANSION; CELL MEDIATED CYTOTOXICITY; CYTOTOXIC T LYMPHOCYTE; DRUG RECEPTOR BINDING; DRUG TARGETING; HUMAN; HUMAN CELL; LYMPHOCYTE ACTIVATION; MAJOR HISTOCOMPATIBILITY COMPLEX; PROTEIN EXPRESSION; SURFACE PLASMON RESONANCE; T LYMPHOCYTE SUBPOPULATION; TUMOR CELL; CYTOTOXICITY; FLOW CYTOMETRY; GENETICS; IMMUNOLOGY; KINETICS; METABOLISM; MOLECULAR CLONING; MOLECULAR MIMICRY; NEOPLASM; T LYMPHOCYTE; T LYMPHOCYTE RECEPTOR GENE; TUMOR CELL LINE;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CLONING, MOLECULAR; CYTOTOXICITY, IMMUNOLOGIC; DNA PRIMERS; ENTEROTOXINS; FLOW CYTOMETRY; GENES, T-CELL RECEPTOR BETA; HUMANS; IMMUNOCONJUGATES; KINETICS; LUCIFERASES; MEMBRANE GLYCOPROTEINS; MOLECULAR MIMICRY; NEOPLASMS; SUPERANTIGENS; SURFACE PLASMON RESONANCE; T-LYMPHOCYTES;

EID: 84886077915     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0079082     Document Type: Article

References (57)

1. Cho HI, Celis E, (2009) Optimized peptide vaccines eliciting extensive CD8 T-cell responses with therapeutic antitumor effects. Cancer Res 69: 9012-9019. doi:10.1158/0008-5472.CAN-09-2019. PubMed: 19903852.
2. Kammertoens T, Blankenstein T, (2009) Making and circumventing tolerance to cancer. Eur J Immunol 39: 2345-2353. doi:10.1002/eji.200939612. PubMed: 19634191.
3. Yee C, Thompson JA, Byrd D, Riddell SR, Roche P, et al. (2002) Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci U S A 99: 16168-16173. doi:10.1073/pnas.242600099. PubMed: 12427970.
4. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, et al. (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298: 850-854. doi:10.1126/science.1076514. PubMed: 12242449.
5. Dudley ME, Gross CA, Langhan MM, Garcia MR, Sherry RM, et al. (2010) CD8+ enriched "young" tumor infiltrating lymphocytes can mediate regression of metastatic melanoma. Clin Cancer Res 16: 6122-6131. doi:10.1158/1078-0432.CCR-10-1297. PubMed: 20668005.
6. Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, Berends-van der Meer DM, et al. (2009) Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med 361: 1838-1847. doi:10.1056/NEJMoa0810097. PubMed: 19890126.
7. Thauland TJ, Parker DC, (2010) Diversity in immunological synapse structure. Immunology 131: 466-472. doi:10.1111/j.1365-2567.2010.03366.x. PubMed: 21039474.
8. Potter TA, Grebe K, Freiberg B, Kupfer A, (2001) Formation of supramolecular activation clusters on fresh ex vivo CD8+ T cells after engagement of the T cell antigen receptor and CD8 by antigen-presenting cells. Proc Natl Acad Sci U S A 98: 12624-12629. doi:10.1073/pnas.221458898. PubMed: 11606747.
9. Stone JD, Chervin AS, Kranz DM, (2009) T-cell receptor binding affinities and kinetics: impact on T-cell activity and specificity. Immunology 126: 165-176. doi:10.1111/j.1365-2567.2008.03015.x. PubMed: 19125887.
10. Wooldridge L, Lissina A, Cole DK, van den Berg HA, Price DA, et al. (2009) Tricks with tetramers: how to get the most from multimeric peptide-MHC. Immunology 126: 147-164. doi:10.1111/j.1365-2567.2008.02848.x. PubMed: 19125886.
11. Altman JD, Moss PA, Goulder PJ, Barouch DH, McHeyzer-Williams MG, et al. (1996) Phenotypic analysis of antigen-specific T lymphocytes. Science 274: 94-96. doi:10.1126/science.274.5284.94. PubMed: 8810254.
12. Sykulev Y, Cohen RJ, Eisen HN, (1995) The law of mass action governs antigen-stimulated cytolytic activity of CD8+ cytotoxic T lymphocytes. Proc Natl Acad Sci U S A 92: 11990-11992. doi:10.1073/pnas.92.26.11990. PubMed: 8618829.
13. Dohlsten M, Hedlund G, Akerblom E, Lando PA, Kalland T, (1991) Monoclonal antibody-targeted superantigens: a different class of anti-tumor agents. Proc Natl Acad Sci U S A 88: 9287-9291. doi:10.1073/pnas.88.20.9287. PubMed: 1924393.
14. Dohlsten M, Abrahmsén L, Björk P, Lando PA, Hedlund G, et al. (1994) Monoclonal antibody-superantigen fusion proteins: tumor-specific agents for T-cell-based tumor therapy. Proc Natl Acad Sci U S A 91: 8945-8949. doi:10.1073/pnas.91.19.8945. PubMed: 8090750.
15. Dohlsten M, Hansson J, Ohlsson L, Litton M, Kalland T, (1995) Antibody-targeted superantigens are potent inducers of tumor-infiltrating T lymphocytes in vivo. Proc Natl Acad Sci U S A 92: 9791-9795. doi:10.1073/pnas.92.21.9791. PubMed: 7568219.
16. Kappler J, Kotzin B, Herron L, Gelfand EW, Bigler RD, et al. (1989) V beta-specific stimulation of human T cells by staphylococcal toxins. Science 244: 811-813. doi:10.1126/science.2524876. PubMed: 2524876.
17. White J, Herman A, Pullen AM, Kubo R, Kappler JW, et al. (1989) The V beta-specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell 56: 27-35. doi:10.1016/0092-8674(89)90980-X. PubMed: 2521300.
18. Janeway CA Jr., Yagi J, Conrad PJ, Katz ME, Jones B, et al. (1989) T-cell responses to Mls and to bacterial proteins that mimic its behavior. Immunol Rev 107: 61-88. doi:10.1111/j.1600-065X.1989.tb00003.x. PubMed: 2522086.
19. Dohlsten M, Lando PA, Hedlund G, Trowsdale J, Kalland T, (1990) Targeting of human cytotoxic T lymphocytes to MHC class II-expressing cells by staphylococcal enterotoxins. Immunology 71: 96-100. PubMed: 2210803.
20. Dohlsten M, Sundstedt A, Björklund M, Hedlund G, Kalland T, (1993) Superantigen-induced cytokines suppress growth of human colon-carcinoma cells. Int J Cancer 54: 482-488. doi:10.1002/ijc.2910540321. PubMed: 8509223.
21. Hedlund G, Dohlsten M, Lando PA, Kalland T, (1990) Staphylococcal enterotoxins direct and trigger CTL killing of autologous HLA-DR+ mononuclear leukocytes and freshly prepared leukemia cells. Cell Immunol 129: 426-434. doi:10.1016/0008-8749(90)90218-G. PubMed: 2383900.
22. Forsberg G, Ohlsson L, Brodin T, Björk P, Lando PA, et al. (2001) Therapy of human non-small-cell lung carcinoma using antibody targeting of a modified superantigen. Br J Cancer 85: 129-136. doi:10.1054/bjoc.2001.1891. PubMed: 11437414.
23. Lando PA, Dohlsten M, Ohlsson L, Kalland T, (1995) Tumor-reactive superantigens suppress tumor growth in humanized SCID mice. Int J Cancer 62: 466-471. doi:10.1002/ijc.2910620418. PubMed: 7635573.
24. Shaw DM, Connolly NB, Patel PM, Kilany S, Hedlund G, et al. (2007) A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma. Br J Cancer 96: 567-574. doi:10.1038/sj.bjc.6603567. PubMed: 17285137.
25. Cheng JD, Babb JS, Langer C, Aamdal S, Robert F, et al. (2004) Individualized patient dosing in phase I clinical trials: the role of escalation with overdose control in PNU-214936. J Clin Oncol 22: 602-609. doi:10.1200/JCO.2004.12.034. PubMed: 14966084.
26. Borghaei H, Alpaugh K, Hedlund G, Forsberg G, Langer C, et al. (2009) Phase I dose escalation, pharmacokinetic and pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and with docetaxel in patients with advanced non-small-cell lung cancer. J Clin Oncol 27: 4116-4123. doi:10.1200/JCO.2008.20.2515. PubMed: 19636016.
27. Robinson MK, Alpaugh RK, Borghaei H, (2010) Naptumomab estafenatox: a new immunoconjugate. Expert Opin Biol Ther 10: 273-279. doi:10.1517/14712590903575620. PubMed: 20053143.
28. Erlandsson E, Andersson K, Cavallin A, Nilsson A, Larsson-Lorek U, et al. (2003) Identification of the antigenic epitopes in staphylococcal enterotoxins A and E and design of a superantigen for human cancer therapy. J Mol Biol 333: 893-905. doi:10.1016/j.jmb.2003.09.009. PubMed: 14583188.
29. Forsberg G, Skartved NJ, Wallén-Ohman M, Nyhlén HC, Behm K, et al. (2010) Naptumomab estafenatox, an engineered antibody-superantigen fusion protein with low toxicity and reduced antigenicity. J Immunother 33: 492-499. doi:10.1097/CJI.0b013e3181d75820. PubMed: 20463598.
30. Arden B, Clark SP, Kabelitz D, Mak TW, (1995) Human T-cell receptor variable gene segment families. Immunogenetics 42: 455-500. PubMed: 8550092.
31. Weiss A, Stobo JD, (1984) Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line. J Exp Med 160: 1284-1299. doi:10.1084/jem.160.5.1284. PubMed: 6208306.
32. Ohashi PS, Mak TW, Van den Elsen P, Yanagi Y, Yoshikai Y, et al. (1985) Reconstitution of an active surface T3/T-cell antigen receptor by DNA transfer. Nature 316: 606-609. doi:10.1038/316606a0. PubMed: 4033759.
33. Rosendahl A, Kristensson K, Riesbeck K, Dohlsten M, (2000) T-cell cytotoxicity assays for studying the functional interaction between the superantigen staphylococcal enterotoxin A and T-cell receptors. Methods Mol Biol 145: 241-257. PubMed: 10820726.
34. Björk P, Jönsson U, Svedberg H, Larsson K, Lind P, et al. (1993) Isolation, partial characterization, and molecular cloning of a human colon adenocarcinoma cell-surface glycoprotein recognized by the C215 mouse monoclonal antibody. J Biol Chem 268: 24232-24241. PubMed: 7693697.
35. Forsberg G, Forsgren M, Jaki M, Norin M, Sterky C, et al. (1997) Identification of framework residues in a secreted recombinant antibody fragment that control production level and localization in Escherichia coli. J Biol Chem 272: 12430-12436. doi:10.1074/jbc.272.19.12430. PubMed: 9139690.
36. Cavallin A, Arozenius H, Kristensson K, Antonsson P, Otzen DE, et al. (2000) The spectral and thermodynamic properties of staphylococcal enterotoxin A, E, and variants suggest that structural modifications are important to control their function. J Biol Chem 275: 1665-1672. doi:10.1074/jbc.275.3.1665. PubMed: 10636860.
37. Boulter JM, Glick M, Todorov PT, Baston E, Sami M, et al. (2003) Stable, soluble T-cell receptor molecules for crystallization and therapeutics. Protein Eng 16: 707-711. doi:10.1093/protein/gzg087. PubMed: 14560057.
38. Frayser M, Sato AK, Xu L, Stern LJ, (1999) Empty and peptide-loaded class II major histocompatibility complex proteins produced by expression in Escherichia coli and folding in vitro. Protein Expr Purif 15: 105-114. doi:10.1006/prep.1998.0987. PubMed: 10024477.
39. Saline M, Rödström KE, Fischer G, Orekhov VY, Karlsson BG, et al. (2010) The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation. Nat Commun 1: 119. doi:10.1038/ncomms1117. PubMed: 21081917.
40. Guillet M, Brouard S, Gagne K, Sébille F, Cuturi MC, et al. (2002) Different qualitative and quantitative regulation of V beta TCR transcripts during early acute allograft rejection and tolerance induction. J Immunol 168: 5088-5095. PubMed: 11994461.
41. (1994) The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50: 760-763. doi:10.1107/S0907444994003112. PubMed: 15299374.
42. Li H, Llera A, Tsuchiya D, Leder L, Ysern X, et al. (1998) Three-dimensional structure of the complex between a T cell receptor beta chain and the superantigen staphylococcal enterotoxin B. Immunity 9: 807-816. doi:10.1016/S1074-7613(00)80646-9. PubMed: 9881971.
43. Petersson K, Thunnissen M, Forsberg G, Walse B, (2002) Crystal structure of a SEA variant in complex with MHC class II reveals the ability of SEA to crosslink MHC molecules. Structure 10: 1619-1626. doi:10.1016/S0969-2126(02)00895-X. PubMed: 12467569.
44. Petersson K, Forsberg G, Walse B, (2004) Interplay between superantigens and immunoreceptors. Scand J Immunol 59: 345-355. doi:10.1111/j.0300-9475.2004.01404.x. PubMed: 15049778.
45. Fraser JD, Proft T, (2008) The bacterial superantigen and superantigen-like proteins. Immunol Rev 225: 226-243. doi:10.1111/j.1600-065X.2008.00681.x. PubMed: 18837785.
46. Irwin MJ, Hudson KR, Fraser JD, Gascoigne NR, (1992) Enterotoxin residues determining T-cell receptor V beta binding specificity. Nature 359: 841-843. doi:10.1038/359841a0. PubMed: 1436060.
47. Sarikonda G, Wang H, Puan KJ, Liu XH, Lee HK, et al. (2008) Photoaffinity antigens for human gammadelta T cells. J Immunol 181: 7738-7750. PubMed: 19017963.
48. Andersen PS, Geisler C, Buus S, Mariuzza RA, Karjalainen K, (2001) Role of the T cell receptor ligand affinity in T cell activation by bacterial superantigens. J Biol Chem 276: 33452-33457. doi:10.1074/jbc.M103750200. PubMed: 11397806.
49. Leder L, Llera A, Lavoie PM, Lebedeva MI, Li H, et al. (1998) A mutational analysis of the binding of staphylococcal enterotoxins B and C3 to the T cell receptor beta chain and major histocompatibility complex class II. J Exp Med 187: 823-833. doi:10.1084/jem.187.6.823. PubMed: 9500785.
50. Dohlsten M, Hedlund G, Kalland T, (1991) Staphylococcal-enterotoxin-dependent cell-mediated cytotoxicity. Immunol Today 12: 147-150. doi:10.1016/S0167-5699(05)80043-X. PubMed: 1878125.
51. Arad G, Levy R, Nasie I, Hillman D, Rotfogel Z, et al. (2011) Binding of superantigen toxins into the CD28 homodimer interface is essential for induction of cytokine genes that mediate lethal shock. PLOS Biol 9: e1001149. PubMed: 21931534.
52. Aleksic M, Dushek O, Zhang H, Shenderov E, Chen JL, et al. (2010) Dependence of T cell antigen recognition on T cell receptor-peptide MHC confinement time. Immunity 32: 163-174. doi:10.1016/j.immuni.2009.11.013. PubMed: 20137987.
53. Govern CC, Paczosa MK, Chakraborty AK, Huseby ES, (2010) Fast on-rates allow short dwell time ligands to activate T cells. Proc Natl Acad Sci U S A 107: 8724-8729. doi:10.1073/pnas.1000966107. PubMed: 20421471.
54. Antonsson P, Wingren AG, Hansson J, Kalland T, Varga M, et al. (1997) Functional characterization of the interaction between the superantigen staphylococcal enterotoxin A and the TCR. J Immunol 158: 4245-4251. PubMed: 9126986.
55. Baeuerle PA, Reinhardt C, (2009) Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res 69: 4941-4944. doi:10.1158/0008-5472.CAN-09-0547. PubMed: 19509221.
56. Liddy N, Bossi G, Adams KJ, Lissina A, Mahon TM, et al. (2012) Monoclonal TCR-redirected tumor cell killing. Nat Med, 18: 980-7. PubMed: 22561687.
57. Dreier T, Lorenczewski G, Brandl C, Hoffmann P, Syring U, et al. (2002) Extremely potent, rapid and costimulation-independent cytotoxic T-cell response against lymphoma cells catalyzed by a single-chain bispecific antibody. Int J Cancer 100: 690-697. doi:10.1002/ijc.10557. PubMed: 12209608.