リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Polymorphic Region-Specific Antibody for Evaluation of Affinity-Associated Profile of Chimeric Antigen Receptor」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Polymorphic Region-Specific Antibody for Evaluation of Affinity-Associated Profile of Chimeric Antigen Receptor

土屋 陽平 髙橋 昌樹 北口 哲也 上田 宏 東京工業大学 DOI:https://doi.org/10.1016/j.omto.2020.04.004

2020.04

概要

Antibody applications in cancer immunotherapy involve diverse strategies, some of which redirect T cell-mediated immunity via engineered antibodies. Affinity is a trait that is crucial for these strategies, as optimal affinity reduces unwanted side effects while retaining therapeutic function. Antibody-antigen pairs possess- ing a broad affinity range are required to define optimal affinity and to investigate the affinity-associated functional profiles of T cell-engaging strategies such as bispecific antibodies and chimeric antigen receptor-engineered T cells. Here, we demon- strate the unique binding characteristic of the developed anti- body clone MVR, which exhibits robust binding to B-lymphoid cell lines. Intriguingly, MVR specifically recognizes the highly polymorphic human leukocyte antigen (HLA)-DR complex and exhibits varying affinities that are dependent upon the HLA- DRB1 allele type. Remarkably, MVR binds to the conformational epitope that consists of two hypervariable regions. As an applica- tion of MVR, we demonstrate an MVR-engineered chimeric an- tigen receptor (CAR) that elicits affinity-dependent function in response to a panel of target cell lines that express different HLA-DRB1 alleles. This tool evaluates the effect of affinity on cytotoxic killing, polyfunctionality, and activation-induced cell death of CAR-engineered T cells. Collectively, MVR exhibits huge potential for the evaluation of the affinity-associated profile of T cells that are redirected by engineered antibodies.

参考文献

1. Weiner, L.M., Surana, R., and Wang, S. (2010). Monoclonal antibodies: versatile plat- forms for cancer immunotherapy. Nat. Rev. Immunol. 10, 317–327.

2. Weiner, L.M., Murray, J.C., and Shuptrine, C.W. (2012). Antibody-based immuno- therapy of cancer. Cell 148, 1081–1084.

3. Zhukovsky, E.A., Morse, R.J., and Maus, M.V. (2016). Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection. Curr. Opin. Immunol. 40, 24–35.

4. Barrett, D.M., Teachey, D.T., and Grupp, S.A. (2014). Toxicity management for pa- tients receiving novel T-cell engaging therapies. Curr. Opin. Pediatr. 26, 43–49.

5. Kroschinsky, F., Stölzel, F., von Bonin, S., Beutel, G., Kochanek, M., Kiehl, M., and Schellongowski, P.; Intensive Care in Hematological and Oncological Patients (iCHOP) Collaborative Group (2017). New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management. Crit. Care 21, 89.

6. Neelapu, S.S., Tummala, S., Kebriaei, P., Wierda, W., Gutierrez, C., Locke, F.L., Komanduri, K.V., Lin, Y., Jain, N., Daver, N., et al. (2018). Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat. Rev. Clin. Oncol. 15, 47–62.

7. Caruso, H.G., Hurton, L.V., Najjar, A., Rushworth, D., Ang, S., Olivares, S., Mi, T., Switzer, K., Singh, H., Huls, H., et al. (2015). Tuning sensitivity of CAR to EGFR den- sity limits recognition of normal tissue while maintaining potent antitumor activity. Cancer Res. 75, 3505–3518.

8. Liu, X., Jiang, S., Fang, C., Yang, S., Olalere, D., Pequignot, E.C., Cogdill, A.P., Li, N., Ramones, M., Granda, B., et al. (2015). Affinity-tuned ErbB2 or EGFR chimeric an- tigen receptor T cells exhibit an increased therapeutic index against tumors in mice. Cancer Res. 75, 3596–3607.

9. Han, C., Sim, S.J., Kim, S.H., Singh, R., Hwang, S., Kim, Y.I., Park, S.H., Kim, K.H., Lee, D.G., Oh, H.S., et al. (2018). Desensitized chimeric antigen receptor T cells selec- tively recognize target cells with enhanced antigen expression. Nat. Commun. 9, 468.

10. Slaga, D., Ellerman, D., Lombana, T.N., Vij, R., Li, J., Hristopoulos, M., Clark, R., Johnston, J., Shelton, A., Mai, E., et al. (2018). Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3. Sci. Transl. Med 10, eaat5775.

11. Chapman, C.J., Zhou, J.X., Gregory, C., Rickinson, A.B., and Stevenson, F.K. (1996). VH and VL gene analysis in sporadic Burkitt’s lymphoma shows somatic hypermu- tation, intraclonal heterogeneity, and a role for antigen selection. Blood 88, 3562– 3568.

12. Fortin, J.S., Cloutier, M., and Thibodeau, J. (2013). Exposing the specific roles of the invariant chain isoforms in shaping the MHC class II peptidome. Front. Immunol. 4, 443.

13. Robinson, J., Halliwell, J.A., Hayhurst, J.D., Flicek, P., Parham, P., and Marsh, S.G. (2015). The IPD and IMGT/HLA database: allele variant databases. Nucleic Acids Res. 43, D423–D431.

14. Günther, S., Schlundt, A., Sticht, J., Roske, Y., Heinemann, U., Wiesmüller, K.H., Jung, G., Falk, K., Rötzschke, O., and Freund, C. (2010). Bidirectional binding of invariant chain peptides to an MHC class II molecule. Proc. Natl. Acad. Sci. USA 107, 22219–22224.

15. Hunter, S.A., and Cochran, J.R. (2016). Cell-binding assays for determining the affin- ity of protein-protein interactions: technologies and considerations. Methods Enzymol. 580, 21–44.

16. Chmielewski, M., Hombach, A.A., and Abken, H. (2011). CD28 cosignalling does not affect the activation threshold in a chimeric antigen receptor-redirected T-cell attack. Gene Ther. 18, 62–72.

17. Drent, E., Themeli, M., Poels, R., de Jong-Korlaar, R., Yuan, H., de Bruijn, J., Martens, A.C.M., Zweegman, S., van de Donk, N.W.C.J., Groen, R.W.J., et al. (2017). A rational strategy for reducing on-target off-tumor effects of CD38-chimeric antigen receptors by affinity optimization. Mol. Ther. 25, 1946–1958.

18. Park, S., Shevlin, E., Vedvyas, Y., Zaman, M., Park, S., Hsu, Y.S., Min, I.M., and Jin, M.M. (2017). Micromolar affinity CAR T cells to ICAM-1 achieves rapid tumor elim- ination while avoiding systemic toxicity. Sci. Rep. 7, 14366.

19. Hudecek, M., Sommermeyer, D., Kosasih, P.L., Silva-Benedict, A., Liu, L., Rader, C., Jensen, M.C., and Riddell, S.R. (2015). The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity. Cancer Immunol. Res. 3, 125–135.

20. Künkele, A., Johnson, A.J., Rolczynski, L.S., Chang, C.A., Hoglund, V., Kelly-Spratt, K.S., and Jensen, M.C. (2015). Functional tuning of CARs reveals signaling threshold above which CD85 CTL antitumor potency is attenuated due to cell Fas–FasL-depen- dent AICD. Cancer Immunol. Res. 3, 368–379.

21. Gomes-Silva, D., Mukherjee, M., Srinivasan, M., Krenciute, G., Dakhova, O., Zheng, Y., Cabral, J.M.S., Rooney, C.M., Orange, J.S., Brenner, M.K., and Mamonkin, M. (2017). Tonic 4-1BB costimulation in chimeric antigen receptors impedes T cell sur- vival and is vector-dependent. Cell Rep. 21, 17–26.

22. Lin, T.S., Stock, W., Xu, H., Phelps, M.A., Lucas, M.S., Guster, S.K., Briggs, B.R., Cheney, C., Porcu, P., Flinn, I.W., et al. (2009). A phase I/II dose escalation study of apolizumab (Hu1D10) using a stepped-up dosing schedule in patients with chronic lymphocytic leukemia and acute leukemia. Leuk. Lymphoma 50, 1958–1963.

23. Schweighofer, C.D., Tuchscherer, A., Sperka, S., Meyer, T., Rattel, B., Stein, S., Ismail, S., Elter, T., Staib, P., Reiser, M., and Hallek, M. (2012). Clinical safety and pharma- cological profile of the HLA-DR antibody 1D09C3 in patients with B cell chronic lymphocytic leukemia and lymphoma: results from a phase I study. Cancer Immunol. Immunother. 61, 2367–2373.

24. Arcangeli, S., Rotiroti, M.C., Bardelli, M., Simonelli, L., Magnani, C.F., Biondi, A., Biagi, E., Tettamanti, S., and Varani, L. (2017). Balance of anti-CD123 chimeric an- tigen receptor binding affinity and density for the targeting of acute myeloid leuke- mia. Mol. Ther. 25, 1933–1945.

25. Long, A.H., Haso, W.M., Shern, J.F., Wanhainen, K.M., Murgai, M., Ingaramo, M., Smith, J.P., Walker, A.J., Kohler, M.E., Venkateshwara, V.R., et al. (2015). 4-1BB cos- timulation ameliorates T cell exhaustion induced by tonic signaling of chimeric an- tigen receptors. Nat. Med. 21, 581–590.

26. Mamonkin, M., Rouce, R.H., Tashiro, H., and Brenner, M.K. (2015). A T-cell- directed chimeric antigen receptor for the selective treatment of T-cell malignancies. Blood 126, 983–992.

27. Ghorashian, S., Kramer, A.M., Onuoha, S., Wright, G., Bartram, J., Richardson, R., Albon, S.J., Casanovas-Company, J., Castro, F., Popova, B., et al. (2019). Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat. Med. 25, 1408–1414.

28. Schubert, I., Kellner, C., Stein, C., Kügler, M., Schwenkert, M., Saul, D., Stockmeyer, B., Berens, C., Oduncu, F.S., Mackensen, A., and Fey, G.H. (2012). A recombinant tri- plebody with specificity for CD19 and HLA-DR mediates preferential binding to an- tigen double-positive cells by dual-targeting. MAbs 4, 45–56.

29. Davenport, A.J., Cross, R.S., Watson, K.A., Liao, Y., Shi, W., Prince, H.M., Beavis, P.A., Trapani, J.A., Kershaw, M.H., Ritchie, D.S., et al. (2018). Chimeric antigen re- ceptor T cells form nonclassical and potent immune synapses driving rapid cytotox- icity. Proc. Natl. Acad. Sci. USA 115, E2068–E2076.

30. Yuan, J., Gnjatic, S., Li, H., Powel, S., Gallardo, H.F., Ritter, E., Ku, G.Y., Jungbluth, A.A., Segal, N.H., Rasalan, T.S., et al. (2008). CTLA-4 blockade enhances polyfunc- tional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clin- ical benefit. Proc. Natl. Acad. Sci. USA 105, 20410–20415.

31. Ding, Z.C., Huang, L., Blazar, B.R., Yagita, H., Mellor, A.L., Munn, D.H., and Zhou, G. (2012). Polyfunctional CD4+ T cells are essential for eradicating advanced B-cell lym- phoma after chemotherapy. Blood 120, 2229–2239.

32. Franzese, O., Palermo, B., Di Donna, C., Sperduti, I., Ferraresi, V., Stabile, H., Gismondi, A., Santoni, A., and Nisticò, P. (2016). Polyfunctional Melan-A-specific tumor-reactive CD8(+) T cells elicited by dacarbazine treatment before peptide- vaccination depends on AKT activation sustained by ICOS. OncoImmunology 5, e1114203.

33. Alabanza, L., Pegues, M., Geldres, C., Shi, V., Wiltzius, J.J.W., Sievers, S.A., Yang, S., and Kochenderfer, J.N. (2017). Function of novel anti-CD19 chimeric antigen recep- tors with human variable regions is affected by hinge and transmembrane domains. Mol. Ther. 25, 2452–2465.

34. Choe, J., Li, L., Zhang, X., Gregory, C.D., and Choi, Y.S. (2000). Distinct role of follic- ular dendritic cells and T cells in the proliferation, differentiation, and apoptosis of a centroblast cell line, L3055. J. Immunol. 164, 56–63.

35. Kim, H.S., Zhang, X., and Choi, Y.S. (1994). Activation and proliferation of follicular dendritic cell-like cells by activated T lymphocytes. J. Immunol. 153, 2951–2961.

36. Shevchenko, A., Wilm, M., Vorm, O., and Mann, M. (1996). Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal. Chem. 68, 850–858.

37. Robinson, J., Halliwell, J.A., McWilliam, H., Lopez, R., and Marsh, S.G. (2013). IPD– the Immuno Polymorphism Database. Nucleic Acids Res. 41, D1234–D1240.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る