Advances in understanding myeloma biology have shown that disease progression is not only the consequence of intrinsic tumor changes but also of interactions between the tumor and the microenvironment in which the cancer grows. The immune system is an important component of the tumor microenvironment in myeloma, and acting on the immune system is an appealing new treatment strategy. There are 2 ways to act toward immune cells and boost antitumor immunity: (1) to increase antitumor activity (acting on T and NK cytotoxic cells), and (2) to reduce immunosuppression (acting on myeloid-derived stem cells and T regulatory cells). Checkpoint inhibitors and adoptive cell therapy (ACT) are 2 of the main actors, together with monoclonal antibodies and immunomodulatory agents, in the immune-oncologic approach. The aim of checkpoint inhibitors is to release the brakes that block the action of the immune system against the tumor. Anti-programmed death-1 (PD-1) and PD-1-Ligand, as well as anti-CTLA4 and KIR are currently under evaluation, as single agents or in combination, with the best results achieved so far with combination of anti–PD-1 and immunomodulatory agents. The aim of ACT is to create an immune effector specific against the tumor. Preliminary results on chimeric antigen receptor (CAR) T cells, first against CD19, and more recently against B-cell maturation antigen, have shown to induce durable responses in heavily pretreated patients. This review focuses on the most recent clinical results available on the use of checkpoint inhibitors and CAR-T cells in myeloma, in the context of the new immune-oncologic approach.

Immuno-oncologic Approaches: CAR-T Cells and Checkpoint Inhibitors

GAY, Francesca Maria
First
;
D'AGOSTINO, MATTIA;GIACCONE, Luisa;GENUARDI, MARIELLA;FESTUCCIA, MORENO BENEDETTO;BOCCADORO, Mario;BRUNO, Benedetto
Last
2017-01-01

Abstract

Advances in understanding myeloma biology have shown that disease progression is not only the consequence of intrinsic tumor changes but also of interactions between the tumor and the microenvironment in which the cancer grows. The immune system is an important component of the tumor microenvironment in myeloma, and acting on the immune system is an appealing new treatment strategy. There are 2 ways to act toward immune cells and boost antitumor immunity: (1) to increase antitumor activity (acting on T and NK cytotoxic cells), and (2) to reduce immunosuppression (acting on myeloid-derived stem cells and T regulatory cells). Checkpoint inhibitors and adoptive cell therapy (ACT) are 2 of the main actors, together with monoclonal antibodies and immunomodulatory agents, in the immune-oncologic approach. The aim of checkpoint inhibitors is to release the brakes that block the action of the immune system against the tumor. Anti-programmed death-1 (PD-1) and PD-1-Ligand, as well as anti-CTLA4 and KIR are currently under evaluation, as single agents or in combination, with the best results achieved so far with combination of anti–PD-1 and immunomodulatory agents. The aim of ACT is to create an immune effector specific against the tumor. Preliminary results on chimeric antigen receptor (CAR) T cells, first against CD19, and more recently against B-cell maturation antigen, have shown to induce durable responses in heavily pretreated patients. This review focuses on the most recent clinical results available on the use of checkpoint inhibitors and CAR-T cells in myeloma, in the context of the new immune-oncologic approach.
2017
17
8
471
478
http://www.sciencedirect.com/science/journal/21522650
https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(17)30709-7/fulltext
https://doi.org/10.1016/j.clml.2017.06.014
CAR-T cells; Checkpoint inhibitors; Chimeric antigen receptor; Immune-oncology; Multiple myeloma; Hematology; Oncology; Cancer Research
Gay, Francesca; D'Agostino, Mattia; Giaccone, Luisa; Genuardi, Mariella; Festuccia, Moreno; Boccadoro, Mario; Bruno, Benedetto
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Descrizione: [Author Vsn.] Gay F et al. Clin Lymphoma Myeloma Leuk . 2017 Aug;17(8):471-478. doi: 10.1016/j.clml.2017.06.014. Epub 2017 Jun 17. © 2017 Elsevier Inc. The published version is available at: https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(17)30709-7/fulltext | https://doi.org/10.1016/j.clml.2017.06.014
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Descrizione: [Restricted access - Published vsn.] Gay F et al. Clin Lymphoma Myeloma Leuk . 2017 Aug;17(8):471-478. doi: 10.1016/j.clml.2017.06.014. Epub 2017 Jun 17. © 2017 Elsevier Inc. Available at: https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(17)30709-7/fulltext | https://doi.org/10.1016/j.clml.2017.06.014
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1649093
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