Overcoming Barriers to Immunotherapy Treatment in AML
DOI:
https://doi.org/10.58445/rars.984Keywords:
AML, Immunotherapy, CAR T cellsAbstract
Acute Myeloid Leukemia (AML) is an aggressive cancer with poor prognosis and limited therapies. In particular, it has met with numerous challenges in the development of promising chimeric antigen receptor (CAR) T cell therapy and other emerging immunotherapies. Current standard of care has a high rate of resistance and relapse. The most significant challenge with CAR T cells is finding a suitable antigen target for AML. Several antigen targets including CD33, CD123, CD7, CLL1, FLT3 have been considered and tested in clinical trials but also have potential problems such as on-target off-tumor toxicity. Additionally, new technologies such as SynNotch CARs, the inducible caspase 9 suicide gene, and bi-specific T cell/NK cell engagers are being introduced to ensure more specific and/or complete eradication of AML.
References
Allen, Cecily, Amer M. Zeidan, and Jan Philipp Bewersdorf. 2021. “Bites, Darts, Bikes and Trikes—Are Antibody Based Therapies Changing the Future Treatment of Aml?” Life. MDPI AG. https://doi.org/10.3390/life11060465.
Ataca Atilla, Pinar, Mary K. McKenna, Haruko Tashiro, Madhuwanti Srinivasan, Feiyan Mo, Norihiro Watanabe, Brian Wesley Simons, et al. 2020. “Modulating Tnfα Activity Allows Transgenic Il15-Expressing Cll-1 Car t Cells to Safely Eliminate Acute Myeloid Leukemia.” Journal for ImmunoTherapy of Cancer 8 (2). https://doi.org/10.1136/jitc-2020-001229.
Bauer, Jens, Annika Nelde, Tatjana Bilich, and Juliane S. Walz. 2019. “Antigen Targets for the Development of Immunotherapies in Leukemia.” International Journal of Molecular Sciences. MDPI AG. https://doi.org/10.3390/ijms20061397.
Brudno, Jennifer N., and James N. Kochenderfer. 2019. “Recent Advances in CAR T-Cell Toxicity: Mechanisms, Manifestations and Management.” Blood Reviews. Churchill Livingstone. https://doi.org/10.1016/j.blre.2018.11.002.
Choe, Joseph H., Payal B. Watchmaker, Milos S. Simic, Ryan D. Gilbert, Aileen W. Li, Nira A. Krasnow, Kira M. Downey, et al. 2021. “SynNotch-CAR T Cells Overcome Challenges of Specificity, Heterogeneity, and Persistence in Treating Glioblastoma.” Science Translational Medicine 13 (591). https://doi.org/10.1126/scitranslmed.abe7378.
Cui, Qingya, Chongsheng Qian, Nan Xu, Liqing Kang, Haiping Dai, Wei Cui, Baoquan Song, et al. 2021. “CD38-Directed CAR-T Cell Therapy: A Novel Immunotherapy Strategy for Relapsed Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation.” Journal of Hematology and Oncology. BioMed Central Ltd. https://doi.org/10.1186/s13045-021-01092-4.
Daver, Naval, Ahmad S. Alotaibi, Veit Bücklein, and Marion Subklewe. 2021. “T-Cell-Based Immunotherapy of Acute Myeloid Leukemia: Current Concepts and Future Developments.” Leukemia. Springer Nature. https://doi.org/10.1038/s41375-021-01253-x.
Daver, Naval, Jorge Cortes, Hagop Kantarjian, and Farhad Ravandi. 2016. “Acute Myeloid Leukemia: Advancing Clinical Trials and Promising Therapeutics.” Expert Review of Hematology. Taylor and Francis Ltd. https://doi.org/10.1586/17474086.2016.1158096.
Daver, Naval, Guillermo Garcia-Manero, Sreyashi Basu, Prajwal C. Boddu, Mansour Alfayez, Jorge E. Cortes, Marina Konopleva, et al. 2019. “Efficacy, Safety, and Biomarkers of Response to Azacitidine and Nivolumab in Relapsed/ Refractory Acute Myeloid Leukemia: A Nonrandomized, Open-Label, Phase II Study.” Cancer Discovery 9 (3): 370–83. https://doi.org/10.1158/2159-8290.CD-18-0774.
Devillier, Raynier, Edouard Forcade, Alice Garnier, Sarah Guenounou, Sylvian Thepot, Gaelle Guillerm, Patrice Ceballos, et al. 2022. “In-Depth Time-Dependent Analysis of the Benefit of Allo-HSCT for Elderly Patients with CR1 AML: A FILO Study.” Blood Advances 6 (6): 1804–12. https://doi.org/10.1182/BLOODADVANCES.2021004435.
Devillier, Raynier, Faezeh Legrand, Jérôme Rey, Luca Castagna, Sabine Fürst, Angela Granata, Aude Charbonnier, et al. 2018. “HLA-Matched Sibling versus Unrelated versus Haploidentical Related Donor Allogeneic Hematopoietic Stem Cell Transplantation for Patients Aged Over 60 Years with Acute Myeloid Leukemia: A Single-Center Donor Comparison.” Biology of Blood and Marrow Transplantation 24 (7): 1449–54. https://doi.org/10.1016/j.bbmt.2018.02.002.
Gomes-Silva, Diogo, Erden Atilla, Pinar Ataca Atilla, Feiyan Mo, Haruko Tashiro, Madhuwanti Srinivasan, Premal Lulla, et al. 2019. “CD7 CAR T Cells for the Therapy of Acute Myeloid Leukemia.” Molecular Therapy 27 (1): 272–80. https://doi.org/10.1016/j.ymthe.2018.10.001.
Gómez-Llobell, Marina, Andrés Peleteiro Raíndo, Jose Climent Medina, Ignacio Gómez Centurión, and Adrián Mosquera Orgueira. 2022. “Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: A Meta-Analysis.” Frontiers in Oncology. Frontiers Media S.A. https://doi.org/10.3389/fonc.2022.882531.
Guercio, Marika, Simona Manni, Iolanda Boffa, Simona Caruso, Stefano di Cecca, Matilde Sinibaldi, Zeinab Abbaszadeh, et al. 2021. “Inclusion of the Inducible Caspase 9 Suicide Gene in CAR Construct Increases Safety of CAR.CD19 T Cell Therapy in B-Cell Malignancies.” Frontiers in Immunology 12 (October). https://doi.org/10.3389/fimmu.2021.755639.
Guinn, Barbara, Barbara-Ann Guinn, Azim Mohamedali, Ken I Mills, Barbara Czepulkowski, Michael Schmitt, and Jochen Greiner. n.d. “Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia.”
http://www.la-press.com/copyright.htm.
Haubner, S., F. Perna, T. Köhnke, C. Schmidt, S. Berman, C. Augsberger, F. M. Schnorfeil, et al.
“Coexpression Profile of Leukemic Stem Cell Markers for Combinatorial Targeted Therapy in AML.” Leukemia 33 (1): 64–74. https://doi.org/10.1038/s41375-018-0180-3.
Hyrenius-Wittsten, Axel, Yang Su, Minhee Park, Julie M. Garcia, Josef Alavi, Nathaniel Perry, Garrett Montgomery, Bin Liu, and Kole T. Roybal. 2021. “SynNotch CAR Circuits Enhance Solid Tumor Recognition and Promote Persistent Antitumor Activity in Mouse Models.” Science Translational Medicine 13 (591). https://doi.org/10.1126/scitranslmed.abd8836.
Isidori, Alessandro, Claudio Cerchione, Naval Daver, Courtney DiNardo, Guillermo
Garcia-Manero, Marina Konopleva, Elias Jabbour, et al. 2021. “Immunotherapy in Acute Myeloid Leukemia: Where We Stand.” Frontiers in Oncology. Frontiers Media S.A. https://doi.org/10.3389/fonc.2021.656218.
Jin, Xin, Meng Zhang, Rui Sun, Hairong Lyu, Xia Xiao, Xiaomei Zhang, Fan Li, et al. 2022. “First-in-Human Phase I Study of CLL-1 CAR-T Cells in Adults with Relapsed/Refractory Acute Myeloid Leukemia.” Journal of Hematology & Oncology 15 (1): 88. https://doi.org/10.1186/s13045-022-01308-1.
Limongello, Roberto, Andrea Marra, Antonella Mancusi, Samanta Bonato, Eni Hoxha, Loredana Ruggeri, Susanta Hui, Andrea Velardi, and Antonio Pierini. 2021. “Novel Immune
Cell-Based Therapies to Eradicate High-Risk Acute Myeloid Leukemia.” Frontiers in Immunology 12 (August). https://doi.org/10.3389/fimmu.2021.695051.
Marofi, Faroogh, Heshu Sulaiman Rahman, Zaid Mahdi Jaber Al-Obaidi, Abduladheem Turki Jalil, Walid Kamal Abdelbasset, Wanich Suksatan, Aleksei Evgenievich Dorofeev, et al. 2021. “Novel CAR T Therapy Is a Ray of Hope in the Treatment of Seriously Ill AML Patients.” Stem Cell Research and Therapy. BioMed Central Ltd. https://doi.org/10.1186/s13287-021-02420-8.
Morris, Emma C., Sattva S. Neelapu, Theodoros Giavridis, and Michel Sadelain. 2022. “Cytokine Release Syndrome and Associated Neurotoxicity in Cancer Immunotherapy.” Nature Reviews Immunology. Nature Research.
https://doi.org/10.1038/s41577-021-00547-6.
Naval G. Daver, Guillermo Garcia-Manero, Marina Y Konopleva, Mansour Alfayez, Naveen Pemmaraju, Tapan M. Kadia, Courtney D. DiNardo, et al. 2019. “Azacitidine (AZA) with Nivolumab (Nivo), and AZA with Nivo + Ipilimumab (Ipi) in Relapsed/Refractory Acute
Myeloid Leukemia: A Non-Randomized, Prospective, Phase 2 Study.” Blood 134 (Supplement_1).
Roerden, Malte, Annika Nelde, and Juliane S. Walz. 2019. “Neoantigens in Hematological Malignancies—Ultimate Targets for Immunotherapy?” Frontiers in Immunology. Frontiers Media S.A. https://doi.org/10.3389/fimmu.2019.03004.
Sommer, Cesar, Hsin Yuan Cheng, Duy Nguyen, Danielle Dettling, Yik Andy Yeung, Janette Sutton, Moustafa Hamze, et al. 2020. “Allogeneic FLT3 CAR T Cells with an Off-Switch Exhibit Potent Activity against AML and Can Be Depleted to Expedite Bone Marrow Recovery.” Molecular Therapy 28 (10): 2237–51. https://doi.org/10.1016/j.ymthe.2020.06.022.
Vago, Luca, and Ivana Gojo. 2020. “Immune Escape and Immunotherapy of Acute Myeloid Leukemia.” Journal of Clinical Investigation 130 (4): 1552–64. https://doi.org/10.1172/JCI129204.
Watanabe, Norihiro, Feiyan Mo, Rong Zheng, Royce Ma, Vanesa C. Bray, Dayenne G. van Leeuwen, Juntima Sritabal-Ramirez, et al. 2022. “Feasibility and Preclinical Efficacy of CD7-Unedited CD7 CAR T Cells for T Cell Malignancies.” Molecular Therapy, September. https://doi.org/10.1016/j.ymthe.2022.09.003.
Zeidner, Joshua F., Benjamin G. Vincent, Anastasia Ivanova, Dominic Moore, Karen P. McKinnon, Alec D. Wilkinson, Rupkatha Mukhopadhyay, et al. 2021. “Phase II Trial of Pembrolizumab after High-Dose Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia.” Blood Cancer Discovery 2 (6): 616–29.
https://doi.org/10.1158/2643-3230.bcd-21-0070.
Zhu, Cheng Ying, Guo Feng Chen, Wei Zhou, Cheng Hou, Xiao Kai Wang, Fei Yan Wang, Nan Yang, et al. 2019. “Outcome and Prognostic Factors of High-Risk Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation.” Annals of Transplantation 24: 328–40. https://doi.org/10.12659/AOT.915381.
Downloads
Posted
Categories
License
Copyright (c) 2024 Medha Nemani, Zachary Reinstein
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.