Development of a Novel CD26-Targeted Chimeric Antigen Receptor T-Cell Therapy for CD26-Expressing T-Cell Malignancies
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Patient Samples
2.3. Ethics Approval and Consent to Participate
2.4. Luciferase-Expression Vector
2.5. Flow Cytometry
2.6. Immunohistochemical Staining
2.7. Construction of CD26 CAR
2.8. Transduction and Expression of CD26 CAR
2.9. Activation of CD26 CAR-T-Cells
2.10. In Vitro Anti-Tumor Activity of CD26 CAR-T-Cells
2.11. In Vivo Anti-Tumor Activity of CD26 CAR-T-Cells
2.12. In Vitro Anti-Tumor Activity of CD26 CAR-T-Cells against Patient Samples
2.13. Statistical Analysis
3. Results
3.1. Transduction and Expression of CD26 CAR
3.2. Expansion of CD26 CAR-T-Cells
3.3. Activation of CD26 CAR-T-Cells
3.4. In Vitro Anti-Tumor Activity of CD26 CAR-T-Cells
3.5. In Vivo Anti-Tumor Activity of CD26 CAR-T-Cells
3.6. Anti-Tumor Activity of CD26 CAR-T-Cells against Patient Samples
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Ohnuma, K.; Hosono, O.; Dang, N.H.; Morimoto, C. Dipeptidyl Peptidase in Autoimmune Pathophysiology. Adv. Clin. Chem. 2011, 53, 51–84. [Google Scholar]
- Thompson, M.; Ohnuma, K.; Abe, M.; Morimoto, C.; Dang, N. CD26/Dipeptidyl Peptidase IV as a Novel Therapeutic Target for Cancer and Immune Disorders. Mini-Rev. Med. Chem. 2007, 7, 253–273. [Google Scholar] [CrossRef] [PubMed]
- Cordero, O.J.; Rafael-Vidal, C.; Varela-Calviño, R.; Calviño-Sampedro, C.; Malvar-Fernández, B.; García, S.; Viñuela, J.E.; Pego-Reigosa, J.M. Distinctive CD26 Expression on CD4 T-Cell Subsets. Biomolecules 2021, 11, 1446. [Google Scholar] [CrossRef] [PubMed]
- Ohnuma, K.; Hatano, R.; Komiya, E.; Otsuka, H.; Itoh, T.; Iwao, N.; Kaneko, Y.; Yamada, T.; Dang, N.H.; Morimoto, C. A Novel Role for CD26/Dipeptidyl Peptidase IV as a Therapeutic Target. Front. Biosci. 2018, 23, 1754–1779. [Google Scholar] [CrossRef] [PubMed]
- Havre, P.A.; Abe, M.; Urasaki, Y.; Ohnuma, K.; Morimoto, C.; Dang, N.H. The Role of CD26/Dipeptidyl Peptidase IV in Cancer. Front. Biosci. 2008, 13, 1345–1351. [Google Scholar] [CrossRef]
- Inamoto, T.; Yamochi, T.; Ohnuma, K.; Iwata, S.; Kina, S.; Inamoto, S.; Tachibana, M.; Katsuoka, Y.; Dang, N.H.; Morimoto, C. Anti-CD26 Monoclonal Antibody-Mediated G1-S Arrest of Human Renal Clear Cell Carcinoma Caki-2 Is Associated with Retinoblastoma Substrate Dephosphorylation, Cyclin-Dependent Kinase 2 Reduction, P27kip1 Enhancement, and Disruption of Binding to the Extracellular Matrix. Clin. Cancer Res. 2006, 12, 3470–3477. [Google Scholar] [PubMed] [Green Version]
- Inamoto, T.; Yamada, T.; Ohnuma, K.; Kina, S.; Takahashi, N.; Yamochi, T.; Inamoto, S.; Katsuoka, Y.; Hosono, O.; Tanaka, H.; et al. Humanized Anti-CD26 Monoclonal Antibody as a Treatment for Malignant Mesothelioma Tumors. Clin. Cancer Res. 2007, 13, 4191–4200. [Google Scholar] [CrossRef] [Green Version]
- Angevin, E.; Isambert, N.; Trillet-Lenoir, V.; You, B.; Alexandre, J.; Zalcman, G.; Vielh, P.; Farace, F.; Valleix, F.; Podoll, T.; et al. First-in-Human Phase 1 of YS110, a Monoclonal Antibody Directed against CD26 in Advanced CD26-Expressing Cancers. Br. J. Cancer 2017, 116, 1126–1137. [Google Scholar] [CrossRef] [Green Version]
- Nakagawa, K.; Kijima, T.; Okada, M.; Morise, M.; Kato, M.; Hirano, K.; Fujimoto, N.; Takenoyama, M.; Yokouchi, H.; Ohe, Y.; et al. Phase 2 Study of YS110, a Recombinant Humanized Anti-CD26 Monoclonal Antibody, in Japanese Patients With Advanced Malignant Pleural Mesothelioma. JTO Clin. Res. Rep. 2021, 2, 100178. [Google Scholar] [CrossRef]
- Takeda, M.; Ohe, Y.; Horinouchi, H.; Hida, T.; Shimizu, J.; Seto, T.; Nosaki, K.; Kishimoto, T.; Miyashita, I.; Yamada, M.; et al. Phase I Study of YS110, a Recombinant Humanized Monoclonal Antibody to CD26, in Japanese Patients with Advanced Malignant Pleural Mesothelioma. Lung Cancer 2019, 137, 64–70. [Google Scholar] [CrossRef]
- Sato, T.; Yamochi, T.; Yamochi, T.; Aytac, U.; Ohnuma, K.; McKee, K.S.; Morimoto, C.; Dang, N.H. CD26 Regulates P38 Mitogen-Activated Protein Kinase-Dependent Phosphorylation of Integrin Β1, Adhesion to Extracellular Matrix, and Tumorigenicity of T-Anaplastic Large Cell Lymphoma Karpas 299. Cancer Res. 2005, 65, 6950–6956. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ho, L.; Aytac, U.; Stephens, L.C.; Ohnuma, K.; Mills, G.B.; McKee, K.S.; Neumann, C.; LaPushin, R.; Cabanillas, F.; Abbruzzese, J.L.; et al. In Vitro and in Vivo Antitumor Effect of the Anti-CD26 Monoclonal Antibody 1F7 on Human CD30+ Anaplastic Large Cell T-Cell Lymphoma Karpas 299. Clin. Cancer Res. 2001, 7, 2031–2040. [Google Scholar] [PubMed]
- Escalón, M.P.; Liu, N.S.; Yang, Y.; Hess, M.; Walker, P.L.; Smith, T.L.; Dang, N.H. Prognostic Factors and Treatment of Patients with T-Cell Non-Hodgkin Lymphoma: The, M.D. Anderson Cancer Center Experience. Cancer 2005, 103, 2091–2098. [Google Scholar] [CrossRef] [PubMed]
- Schuster, S.J.; Tam, C.S.; Borchmann, P.; Worel, N.; McGuirk, J.P.; Holte, H.; Waller, E.K.; Jaglowski, S.; Bishop, M.R.; Damon, L.E.; et al. Long-Term Clinical Outcomes of Tisagenlecleucel in Patients with Relapsed or Refractory Aggressive B-Cell Lymphomas (JULIET): A Multicentre, Open-Label, Single-Arm, Phase 2 Study. Lancet Oncol. 2021, 22, 1403–1405. [Google Scholar] [CrossRef] [PubMed]
- Flugel, C.L.; Majzner, R.G.; Krenciute, G.; Dotti, G.; Riddell, S.R.; Wagner, D.L.; Abou-el-Enein, M. Overcoming On-Target, off-Tumour Toxicity of CAR T Cell Therapy for Solid Tumours. Nat. Rev. Clin. Oncol. 2023, 20, 49–62. [Google Scholar] [CrossRef] [PubMed]
- Safarzadeh Kozani, P.; Safarzadeh Kozani, P.; Rahbarizadeh, F. CAR-T Cell Therapy in T-Cell Malignancies: Is Success a Low-Hanging Fruit? Stem Cell Res. Ther. 2021, 12, 527. [Google Scholar] [CrossRef]
- Fleischer, L.C.; Spencer, H.T.; Raikar, S.S. Targeting T Cell Malignancies Using CAR-Based Immunotherapy: Challenges and Potential Solutions. J. Hematol. Oncol. 2019, 12, 141. [Google Scholar] [CrossRef] [Green Version]
- Safarzadeh Kozani, P.; Safarzadeh Kozani, P.; Rahbarizadeh, F. Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward. Front. Immunol. 2021, 12, 765097. [Google Scholar] [CrossRef]
- Mohanty, R.; Chowdhury, C.R.; Arega, S.; Sen, P.; Ganguly, P.; Ganguly, N. CAR T Cell Therapy: A New Era for Cancer Treatment (Review). Oncol. Rep. 2019, 42, 2183–2195. [Google Scholar] [CrossRef]
- Rinaldi, I.; Muthalib, A.; Edina, B.C.; Wiyono, L.; Winston, K. Role of Anti-B-Cell Maturation Antigen (BCMA) in the Management of Multiple Myeloma. Cancers 2022, 14, 3507. [Google Scholar] [CrossRef]
- Barros, L.R.C.; Couto, S.C.F.; da Silva Santurio, D.; Paixão, E.A.; Cardoso, F.; da Silva, V.J.; Klinger, P.; Ribeiro, P.d.A.C.; Rós, F.A.; Oliveira, T.G.M.; et al. Systematic Review of Available CAR-T Cell Trials around the World. Cancers 2022, 14, 2667. [Google Scholar] [CrossRef] [PubMed]
- Ramos, C.A.; Rouce, R.; Robertson, C.S.; Reyna, A.; Narala, N.; Vyas, G.; Mehta, B.; Zhang, H.; Dakhova, O.; Carrum, G.; et al. In Vivo Fate and Activity of Second- versus Third-Generation CD19-Specific CAR-T Cells in B Cell Non-Hodgkin’s Lymphomas. Mol. Ther. 2018, 26, 2727–2737. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aytac, U.; Claret, F.X.; Ho, L.; Sato, K.; Ohnuma, K.; Mills, G.B.; Cabanillas, F.; Morimoto, C.; Dang, N.H. Expression of CD26 and Its Associated Dipeptidyl Peptidase IV Enzyme Activity Enhances Sensitivity to Doxorubicin-Induced Cell Cycle Arrest at the G(2)/M Checkpoint. Cancer Res. 2001, 61, 7204–7210. [Google Scholar]
- Aytac, U.; Sato, K.; Yamochi, T.; Yamochi, T.; Ohnuma, K.; Mills, G.B.; Morimoto, C.; Dang, N.H. Effect of CD26/Dipeptidyl Peptidase IV on Jurkat Sensitivity to G2/M Arrest Induced by Topoisomerase II Inhibitors. Br. J. Cancer 2003, 88, 455–462. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hatano, R.; Yamada, T.; Madokoro, H.; Otsuka, H.; Komiya, E.; Itoh, T.; Narita, Y.; Iwata, S.; Yamazaki, H.; Matsuoka, S.; et al. Development of Novel Monoclonal Antibodies with Specific Binding Affinity for Denatured Human CD26 in Formalin-Fixed Paraffinembedded and Decalcified Specimens. PLoS ONE 2019, 14, e0218330. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fedchenko, N.; Reifenrath, J. Different Approaches for Interpretation and Reporting of Immunohistochemistry Analysis Results in the Bone Tissue—A Review. Diagn. Pathol. 2014, 9, 221. [Google Scholar] [CrossRef] [Green Version]
- Kobayashi, E.; Kishi, H.; Ozawa, T.; Hamana, H.; Nakagawa, H.; Jin, A.; Lin, Z.; Muraguchi, A. A Chimeric Antigen Receptor for TRAIL-Receptor 1 Induces Apoptosis in Various Types of Tumor Cells. Biochem. Biophys. Res. Commun. 2014, 453, 798–803. [Google Scholar] [CrossRef]
- Ono, K.; Sato, T.; Iyama, S.; Tatekoshi, A.; Hashimoto, A.; Kamihara, Y.; Horiguchi, H.; Kikuchi, S.; Kawano, Y.; Takada, K.; et al. A Novel Strategy Inducing Autophagic Cell Death in Burkitt’s Lymphoma Cells with Anti-CD19-Targeted Liposomal Rapamycin. Blood Cancer J. 2014, 4, e180. [Google Scholar] [CrossRef] [Green Version]
- Sato, T.; Tatekoshi, A.; Takada, K.; Iyama, S.; Kamihara, Y.; Jawaid, P.; Rehman, M.U.; Noguchi, K.; Kondo, T.; Kajikawa, S.; et al. DPP8 Is a Novel Therapeutic Target for Multiple Myeloma. Sci. Rep. 2019, 9, 18094. [Google Scholar] [CrossRef] [Green Version]
- Mamonkin, M.; Mukherjee, M.; Srinivasan, M.; Sharma, S.; Gomes-Silva, D.; Mo, F.; Krenciute, G.; Orange, J.S.; Brenner, M.K. Reversible Transgene Expression Reduces Fratricide and Permits 4-1BB Costimulation of CAR T Cells Directed to T-Cell Malignancies. Cancer Immunol. Res. 2018, 6, 47–58. [Google Scholar] [CrossRef] [Green Version]
- Zhou, S.; Zhu, X.; Shen, N.; Li, Q.; Wang, N.; You, Y.; Zhong, Z.; Cheng, F.; Zou, P.; Zhu, X. T Cells Expressing CD26-Specific Chimeric Antigen Receptors Exhibit Extensive Self-Antigen-Driven Fratricide. Immunopharmacol. Immunotoxicol. 2019, 41, 490–496. [Google Scholar] [CrossRef] [PubMed]
- Mamonkin, M.; Rouce, R.H.; Tashiro, H.; Brenner, M.K. A T-Cell-Directed Chimeric Antigen Receptor for the Selective Treatment of T-Cell Malignancies. Blood 2015, 126, 983–992. [Google Scholar] [CrossRef]
- Flavell, D.J.; Boehm, D.A.; Okayama, K.; Kohler, J.A.; Flavell, S.N.U. Therapy of Human T-cell Acute Lymphoblastic Leukaemia in Severe Combined Immunodeficient Mice with Two Different Anti-CD7-saporin Immunotoxins Containing Hindered or Non-hindered Disulphide Cross-linkers. Int. J. Cancer 1994, 58, 407–414. [Google Scholar] [CrossRef] [PubMed]
- Enblad, G.; Karlsson, H.; Gammelgård, G.; Wenthe, J.; Lövgren, T.; Amini, R.M.; Wikstrom, K.I.; Essand, M.; Savoldo, B.; Hallböök, H.; et al. A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. Clin. Cancer Res. 2018, 24, 6185–6194. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, J.; Jensen, M.; Lin, Y.; Sui, X.; Chen, E.; Lindgren, C.G.; Till, B.; Raubitschek, A.; Forman, S.J.; Qian, X.; et al. Optimizing Adoptive Polyclonal T Cell Immunotherapy of Lymphomas, Using a Chimeric T Cell Receptor Possessing CD28 and CD137 Costimulatory Domains. Hum. Gene Ther. 2007, 18, 712–725. [Google Scholar] [CrossRef]
- Zhou, S.; Li, W.; Xiao, Y.; Zhu, X.; Zhong, Z.; Li, Q.; Cheng, F.; Zou, P.; You, Y.; Zhu, X. A Novel Chimeric Antigen Receptor Redirecting T-Cell Specificity towards CD26+ Cancer Cells. Leukemia 2021, 35, 119–129. [Google Scholar] [CrossRef]
- Yamada, K.; Hayashi, M.; Madokoro, H.; Nishida, H.; Du, W.; Ohnuma, K.; Sakamoto, M.; Morimoto, C.; Yamada, T. Nuclear Localization of CD26 Induced by a Humanized Monoclonal Antibody Inhibits Tumor Cell Growth by Modulating of POLR2A Transcription. PLoS ONE 2013, 8, e62304. [Google Scholar] [CrossRef]
- Dang, N.H.; Torimoto, Y.; Sugita, K.; Daley, J.F.; Schow, P.; Prado, C.; Schlossman, S.F.; Morimoto, C. Cell Surface Modulation of CD26 by Anti-1F7 Monoclonal Antibody. Analysis of Surface Expression and Human T Cell Activation. J. Immunol. 1990, 145, 3963–3971. [Google Scholar] [CrossRef]
- Hegen, M.; Kameoka, J.; Dong, R.P.; Schlossman, S.F.; Morimoto, C. Cross-Linking of CD26 Antibody Induces Tyrosine Phosphorylation and Activation of Mitogen-Activated Protein Kinase. Immunology 1997, 90, 257–264. [Google Scholar] [CrossRef]
- Morimoto, C.; Torimoto, Y.; Levinson, G.; Rudd, C.E.; Schrieber, M.; Dang, N.H.; Letvin, N.L.; Schlossman, S.F. 1F7, a Novel Cell Surface Molecule, Involved in Helper Function of CD4 Cells. J. Immunol. 1989, 143, 3430–3439. [Google Scholar] [CrossRef]
- Ohnuma, K.; Takahashi, N.; Yamochi, T.; Hosono, O.; Dang, N.H.; Morimoto, C. Role of CD26/Dipeptidyl Peptidase IV in Human T Cell Activation and Function. Front. Biosci. 2008, 13, 2299–2310. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tanaka, T.; Camerini, D.; Seed, B.; Torimoto, Y.; Dang, N.H.; Kameoka, J.; Dahlberg, H.N.; Schlossman, S.F.; Morimoto, C. Cloning and Functional Expression of the T Cell Activation Antigen CD26. J. Immunol. 1992, 149, 2090. [Google Scholar] [CrossRef]
- Philipson, B.I.; O’Connor, R.S.; May, M.J.; June, C.H.; Albelda, S.M.; Milone, M.C. 4-1BB Costimulation Promotes CAR T Cell Survival through Noncanonical NF-ΚB Signaling. Sci. Signal. 2020, 13, eaay8248. [Google Scholar] [CrossRef]
- Zhao, X.; Yang, J.; Zhang, X.; Lu, X.A.; Xiong, M.; Zhang, J.; Zhou, X.; Qi, F.; He, T.; Ding, Y.; et al. Efficacy and Safety of CD28- or 4-1BB-Based CD19 CAR-T Cells in B Cell Acute Lymphoblastic Leukemia. Mol. Ther.-Oncolytics 2020, 18, 272–281. [Google Scholar] [CrossRef] [PubMed]
- Pan, J.; Tan, Y.; Wang, G.; Deng, B.; Ling, Z.; Song, W.; Seery, S.; Zhang, Y.; Peng, S.; Xu, J.; et al. Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial. J. Clin. Oncol. 2021, 39, 3340–3351. [Google Scholar] [CrossRef]
- Polgárová, K.; Otáhal, P.; Šálek, C.; Pytlík, R. Chimeric Antigen Receptor Based Cellular Therapy for Treatment Of T-Cell Malignancies. Front. Oncol. 2022, 12, 876758. [Google Scholar] [CrossRef]
- Su, A.I.; Wiltshire, T.; Batalov, S.; Lapp, H.; Ching, K.A.; Block, D.; Zhang, J.; Soden, R.; Hayakawa, M.; Kreiman, G.; et al. A Gene Atlas of the Mouse and Human Protein-Encoding Transcriptomes. Proc. Natl. Acad. Sci. USA 2004, 101, 6062–6067. [Google Scholar] [CrossRef] [PubMed]
- Florentin, M.; Kostapanos, M.S.; Papazafiropoulou, A.K. Role of Dipeptidyl Peptidase 4 Inhibitors in the New Era of Antidiabetic Treatment. World J. Diabetes 2022, 13, 85–96. [Google Scholar] [CrossRef]
Negative | Positive | |||
---|---|---|---|---|
Mild | Moderate | Strong | ||
ALCL (n = 2) | 0 | 0 | 2 | 0 |
AITL (n = 4) | 0 | 0 | 4 | 0 |
NK/T (n = 5) | 0 | 3 | 0 | 2 |
PTCL (n = 10) | 0 | 2 | 3 | 5 |
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Kobayashi, E.; Kamihara, Y.; Arai, M.; Wada, A.; Kikuchi, S.; Hatano, R.; Iwao, N.; Susukida, T.; Ozawa, T.; Adachi, Y.; et al. Development of a Novel CD26-Targeted Chimeric Antigen Receptor T-Cell Therapy for CD26-Expressing T-Cell Malignancies. Cells 2023, 12, 2059. https://doi.org/10.3390/cells12162059
Kobayashi E, Kamihara Y, Arai M, Wada A, Kikuchi S, Hatano R, Iwao N, Susukida T, Ozawa T, Adachi Y, et al. Development of a Novel CD26-Targeted Chimeric Antigen Receptor T-Cell Therapy for CD26-Expressing T-Cell Malignancies. Cells. 2023; 12(16):2059. https://doi.org/10.3390/cells12162059
Chicago/Turabian StyleKobayashi, Eiji, Yusuke Kamihara, Miho Arai, Akinori Wada, Shohei Kikuchi, Ryo Hatano, Noriaki Iwao, Takeshi Susukida, Tatsuhiko Ozawa, Yuichi Adachi, and et al. 2023. "Development of a Novel CD26-Targeted Chimeric Antigen Receptor T-Cell Therapy for CD26-Expressing T-Cell Malignancies" Cells 12, no. 16: 2059. https://doi.org/10.3390/cells12162059