TCR-engineered T cells: A model of inducible TCR expression to dissect the interrelationship between two TCRs

European Journal of Immunology

Volumn 44, Issue 1, 2014, Pages 265-274

  Reuß, Simone ^a   Sebestyén, Zsolt ^b,f   Heinz, Niels ^c   Loew, Rainer ^d   Baum, Christopher ^c   Debets, Reno ^b   Uckert, Wolfgang ^a,e  

^a MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^b ERASMUS MEDICAL CENTER   (Netherlands)

^c HANNOVER MEDICAL SCHOOL   (Germany)

^d BIONTECH AG   (Germany)

^e HUMBOLDT UNIVERSITY   (Germany)

^f UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

Fluorescence resonance energy transfer (FRET); Inducible gene expression; TCR gene optimization; TCR gene therapy; TCR mispairing

Indexed keywords

CYSTEINE; DIMER; GAMMA INTERFERON; INTERLEUKIN 2; RETROVIRUS VECTOR; T LYMPHOCYTE RECEPTOR; LYMPHOCYTE ANTIGEN RECEPTOR; REPRESSOR PROTEIN; TETRACYCLINE RESISTANCE-ENCODING TRANSPOSON REPRESSOR PROTEIN;

ANIMAL CELL; ARTICLE; CELL SURFACE; CODON; CONTROLLED STUDY; CYTOKINE RELEASE; FLUORESCENCE RESONANCE ENERGY TRANSFER; GENETIC ENGINEERING; LONG TERMINAL REPEAT; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; RETROVIRUS; SPLEEN CELL; T LYMPHOCYTE; ADOPTIVE IMMUNOTHERAPY; CELL ENGINEERING; DIMERIZATION; GENE EXPRESSION REGULATION; GENE VECTOR; GENETICS; HUMAN; IMMUNOLOGY; JURKAT CELL LINE; METABOLISM; PROCEDURES; PROTEIN ENGINEERING; STRUCTURE ACTIVITY RELATION; TRANSGENE; TRANSPLANTATION;

CELL ENGINEERING; DIMERIZATION; FLUORESCENCE RESONANCE ENERGY TRANSFER; GENE EXPRESSION REGULATION; GENETIC VECTORS; HUMANS; IMMUNOTHERAPY, ADOPTIVE; JURKAT CELLS; PROTEIN ENGINEERING; RECEPTORS, ANTIGEN, T-CELL; REPRESSOR PROTEINS; RETROVIRIDAE; STRUCTURE-ACTIVITY RELATIONSHIP; T-LYMPHOCYTES; TRANSGENES;

EID: 84892473328     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201343591     Document Type: Article

References (40)

1. Robbins, P. F., Morgan, R. A., Feldman, S. A., Yang, J. C., Sherry, R. M., Dudley, M. E., Wunderlich, J. R. et al., Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J. Clin. Oncol. 2011. 29: 917-924.
2. Morgan, R. A., Dudley, M. E., Wunderlich, J. R., Hughes, M. S., Yang, J. C., Sherry, R. M., Royal, R. E. et al., Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006. 314: 126-129.
3. Johnson, L. A., Morgan, R. A., Dudley, M. E., Cassard, L., Yang, J. C., Hughes, M. S., Kammula, U. S. et al., Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 2009. 114: 535-546.
4. Parkhurst, M. R., Yang, J. C., Langan, R. C., Dudley, M. E., Nathan, D.-A. N., Feldman, S. A., Davis, J. L. et al., T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol. Ther. 2011. 19: 620-626.
5. Bendle, G. M., Linnemann, C., Hooijkaas, A. I., Bies, L., de Witte, M. A., Jorritsma, A., Kaiser, A. D. M. et al., Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat. Med. 2010. 16: 565-570.
6. van Loenen, M. M., de Boer, R., Amir, A. L., Hagedoorn, R. S., Volbeda, G. L., Willemze, R., van Rood, J. J. et al., Mixed T cell receptor dimers harbor potentially harmful neoreactivity. Proc. Natl. Acad. Sci. USA 2010. 107: 10972-10977.
7. Scholten, K. B. J., Kramer, D., Kueter, E. W. M., Graf, M., Schoedl, T., Meijer, C. J. L. M., Schreurs, M. W. J. et al., Codon modification of T cell receptors allows enhanced functional expression in transgenic human T cells. Clin. Immunol. 2006. 119: 135-145.
8. Leisegang, M., Engels, B., Meyerhuber, P., Kieback, E., Sommermeyer, D., Xue, S.-A., Reuß, S. et al., Enhanced functionality of T cell receptor-redirected T cells is defined by the transgene cassette. J. Mol. Med. 2008. 86: 573-583.
9. Xue, S.-A., Gao, L., Thomas, S., Hart, D. P., Xue, J. Z., Gillmore, R., Voss, R.-H. et al., Development of a Wilms' tumor antigen-specific T-cell receptor for clinical trials: engineered patient's T cells can eliminate autologous leukemia blasts in NOD/SCID mice. Haematologica 2010. 95: 126-134.
10. Willemsen, R. A., Weijtens, M. E., Ronteltap, C., Eshhar, Z., Gratama, J. W., Chames, P. and Bolhuis, R., Grafting primary human T lymphocytes with cancer-specific chimeric single chain and two chain TCR. Gene Ther. 2000. 7: 1369-1377.
11. Sebestyén, Z., Schooten, E., Sals, T., Zaldivar, I., San José, E., Alarcón, B., Bobisse, S. et al., Human TCR that incorporate CD3ζ induce highly preferred pairing between TCRα and β chains following gene transfer. J. Immunol. 2008. 180: 7736-7746.
12. Cohen, C. J., Zhao, Y., Zheng, Z., Rosenberg, S. A. and Morgan, R. A., Enhanced antitumor activity of murine-human hybrid T-cell receptor (TCR) in human lymphocytes is associated with improved pairing and TCR/CD3 stability. Cancer Res. 2006. 66: 8878-8886.
13. Kuball, J., Dossett, M. L., Wolfl, M., Ho, W. Y., Voss, R.-H., Fowler, C. and Greenberg, P. D., Facilitating matched pairing and expression of TCR chains introduced into human T cells. Blood 2007. 109: 2331-2338.
14. Cohen, C. J., Li, Y. F., El-Gamil, M., Robbins, P. F., Rosenberg, S. A. and Morgan, R. A., Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond. Cancer Res. 2007. 67: 3898-3903.
15. Voss, R.-H., Willemsen, R. A., Kuball, J., Grabowski, M., Engel, R., Intan, R. S., Guillaume, P. et al., Molecular design of the Cαβ interface favors specific pairing of introduced TCRαβ in human T cells. J. Immunol. 2008. 180: 391-401.
16. Aggen, D. H., Chervin, A. S., Schmitt, T. M., Engels, B., Stone, J. D., Richman, S. A., Piepenbrink, K. H. et al., Single-chain V[alpha]V[beta] T-cell receptors function without mispairing with endogenous TCR chains. Gene Ther. 2012. 19: 365-374.
17. Govers, C., Sebestyén, Z., Coccoris, M., Willemsen, R. A. and Debets, R., T cell receptor gene therapy: strategies for optimizing transgenic TCR pairing. Trends Mol. Med. 2010. 16: 77-87.
18. Bialer, G., Horovitz-Fried, M., Ya'acobi, S., Morgan, R. A. and Cohen, C. J., Selected murine residues endow human TCR with enhanced tumor recognition. J. Immunol. 2010. 184: 6232-6241.
19. Sommermeyer, D. and Uckert, W., Minimal amino acid exchange in human TCR constant regions fosters improved function of TCR gene-modified T cells. J. Immunol. 2010. 184: 6223-6231.
20. Heinz, N., Schambach, A., Galla, M., Maetzig, T., Baum, C., Loew, R. and Schiedlmeier, B., Retroviral and transposon-based Tet-regulated all-in-one vectors with reduced background expression and improved dynamic range. Hum. Gene Ther. 2011. 22: 166-176.
21. Letourneur, F. and Malissen, B., Derivation of a T cell hybridoma variant deprived of functional T cell receptor α and β chain transcripts reveals a nonfunctional α-mRNA of BW5147 origin. Eur. J. Immunol. 1989. 19: 2269-2274.
22. Engels, B., Cam, H., Schüler, T., Indraccolo, S., Gladow, M., Baum, C., Blankenstein, T. et al., Retroviral vectors for high-level transgene expression in T lymphocytes. Hum. Gene Ther. 2003. 14: 1155-1168.
23. Sommermeyer, D., Neudorfer, J., Weinhold, M., Leisegang, M., Engels, B., Noessner, E., Heemskerk, M. H. M. et al., Designer T cells by T cell receptor replacement. Eur. J. Immunol. 2006. 36: 3052-3059.
24. Fossati, G., Cooke, A., Papafio, R. Q., Haskins, K. and Stockinger, B., Triggering a second T cell receptor on diabetogenic T cells can prevent induction of diabetes. J. Exp. Med. 1999. 190: 577-584.
25. Gladow, M., Uckert, W. and Blankenstein, T., Dual T cell receptor T cells with two defined specificities mediate tumor suppression via both receptors. Eur. J. Immunol. 2004. 34: 1882-1891.
26. Weinhold, M., Sommermeyer, D., Uckert, W. and Blankenstein, T., Dual T cell receptor expressing CD8+ T cells with tumor- and self-specificity can inhibit tumor growth without causing severe autoimmunity. J. Immunol. 2007. 179: 5534-5542.
27. Jorritsma, A., Gomez-Eerland, R., Dokter, M., van de Kasteele, W., Zoet, Y. M., Doxiadis, I. I. N., Rufer, N. et al., Selecting highly affine and well-expressed TCRs for gene therapy of melanoma. Blood 2007. 110: 3564-3572.
28. Abad, J. D., Wrzensinski, C., Overwijk, W., De Witte, M. A., Jorritsma, A., Hsu, C., Gattinoni, L. et al., T-cell receptor gene therapy of established tumors in a murine melanoma model. J. Immunother. 2008. 31: 1-6. doi: 10.1097/CJI.1090b1013e31815c31193f.
29. Shao, H., Zhang, W., Hu, Q., Wu, F., Shen, H. and Huang, S., TCR mispairing in genetically modified T cells was detected by fluorescence resonance energy transfer. Mol. Biol. Rep. 2010. 37: 3951-3956.
30. Heemskerk, M. H. M., Hagedoorn, R. S., van der Hoorn, M. A. W. G., van der Veken, L. T., Hoogeboom, M., Kester, M. G. D., Willemze, R. et al., Efficiency of T-cell receptor expression in dual-specific T cells is controlled by the intrinsic qualities of the TCR chains within the TCR-CD3 complex. Blood 2007. 109: 235-243.
31. Thomas, S., Xue, S.-A., Cesco-Gaspere, M., San José, E., Hart, D. P., Wong, V., Debets, R. et al., Targeting the Wilms tumor antigen 1 by TCR gene transfer: TCR variants improve tetramer binding but not the function of gene modified human T cells. J. Immunol. 2007. 179: 5803-5810.
32. Okamoto, S., Mineno, J., Ikeda, H., Fujiwara, H., Yasukawa, M., Shiku, H. and Kato, I., Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR. Cancer Res. 2009. 69: 9003-9011.
33. Ochi, T., Fujiwara, H., Okamoto, S., An, J., Nagai, K., Shirakata, T., Mineno, J. et al., Novel adoptive T-cell immunotherapy using a WT1-specific TCR vector encoding silencers for endogenous TCRs shows marked anti-leukemia reactivity and safety. Blood 2011. 118: 1495-1503.
34. Provasi, E., Genovese, P., Lombardo, A., Magnani, Z., Liu, P.-Q., Reik, A., Chu, V. et al., Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat. Med. 2012. 18: 807-815.
35. Morita S., Kojima T. and Kitamura, T., Plat-E: an efficient and stable system for transient packaging of retroviruses. Gene Ther. 2000. 7: 1063-1066.
36. Arden, B., Clark, S. P., Kabelitz, D. and Mak, T. W., Mouse T-cell receptor variable gene segment families. Immunogenetics 1995. 42: 501-530.
37. Kieback, E., Charo, J., Sommermeyer, D., Blankenstein, T. and Uckert, W., A safeguard eliminates T cell receptor gene-modified autoreactive T cells after adoptive transfer. Proc. Natl. Acad. Sci. USA 2008. 105: 623-628.
38. Schüler, T. and Blankenstein, T., Cutting edge: CD8+ effector T cells reject tumors by direct antigen recognition but indirect action on host cells. J. Immunol. 2003. 170: 4427-4431.
39. Hogquist, K. A., Jameson, S. C., Heath, W. R., Howard, J. L., Bevan, M. J. and Carbone, F. R., T cell receptor antagonist peptides induce positive selection. Cell 1994. 76: 17-27.
40. Szentesi, G., Horváth, G., Bori, I., Vámosi, G., Szöllo{double acute}si, J., Gáspár, R., Damjanovich, S. et al., Computer program for determining fluorescence resonance energy transfer efficiency from flow cytometric data on a cell-by-cell basis. Comput. Methods Programs Biomed. 2004. 75: 201-211.