The advent of CAR T-cell therapy for lymphoproliferative neoplasms: Integrating research into clinical practice Review
| Authors: | Cerrano, M.; Ruella, M.; Perales, M. A.; Vitale, C.; Faraci, D. G.; Giaccone, L.; Coscia, M.; Maloy, M.; Sanchez-Escamilla, M.; Elsabah, H.; Fadul, A.; Maffini, E.; Pittari, G.; Bruno, B. |
| Review Title: | The advent of CAR T-cell therapy for lymphoproliferative neoplasms: Integrating research into clinical practice |
| Abstract: | Research on CAR T cells has achieved enormous progress in recent years. After the impressive results obtained in relapsed and refractory B-cell acute lymphoblastic leukemia and aggressive B-cell lymphomas, two constructs, tisagenlecleucel and axicabtagene ciloleucel, were approved by FDA. The role of CAR T cells in the treatment of B-cell disorders, however, is rapidly evolving. Ongoing clinical trials aim at comparing CAR T cells with standard treatment options and at evaluating their efficacy earlier in the disease course. The use of CAR T cells is still limited by the risk of relevant toxicities, most commonly cytokine release syndrome and neurotoxicity, whose management has nonetheless significantly improved. Some patients do not respond or relapse after treatment, either because of poor CAR T-cell expansion, lack of anti-tumor effects or after the loss of the target antigen on tumor cells. Investigators are trying to overcome these hurdles in many ways: by testing constructs which target different and/or multiple antigens or by improving CAR T-cell structure with additional functions and synergistic molecules. Alternative cell sources including allogeneic products (off-the-shelf CAR T cells), NK cells, and T cells obtained from induced pluripotent stem cells are also considered. Several trials are exploring the curative potential of CAR T cells in other malignancies, and recent data on multiple myeloma and chronic lymphocytic leukemia are encouraging. Given the likely expansion of CAR T-cell indications and their wider availability over time, more and more highly specialized clinical centers, with dedicated clinical units, will be required. Overall, the costs of these cell therapies will also play a role in the sustainability of many health care systems. This review will focus on the major clinical trials of CAR T cells in B-cell malignancies, including those leading to the first FDA approvals, and on the new settings in which these constructs are being tested. Besides, the most promising approaches to improve CAR T-cell efficacy and early data on alternative cell sources will be reviewed. Finally, we will discuss the challenges and the opportunities that are emerging with the advent of CAR T cells into clinical routine. © Copyright © 2020 Cerrano, Ruella, Perales, Vitale, Faraci, Giaccone, Coscia, Maloy, Sanchez-Escamilla, Elsabah, Fadul, Maffini, Pittari and Bruno. |
| Keywords: | event free survival; leukemia; overall survival; review; nonhuman; neurotoxicity; clinical practice; neoplasm; lymphocyte proliferation; biological marker; interleukin 2; unindexed drug; progression free survival; multiple myeloma; transforming growth factor beta; blood toxicity; cd40 ligand; granulocyte macrophage colony stimulating factor; interleukin 21; pneumocystis pneumonia; antineoplastic activity; cytotoxicity; risk factor; acute lymphoblastic leukemia; tumor lysis syndrome; b cell lymphoma; cd20 antigen; nonhodgkin lymphoma; gamma interferon; lymphoma; interleukin 6; chimeric antigen receptor; health care system; effector cell; lymphoproliferative disease; pancytopenia; cytokine release; chronic lymphatic leukemia; immunoglobulin kappa chain; immunoglobulin deficiency; beta catenin; wnt protein; cytopenia; adoptive immunotherapy; interleukin 12; interleukin 15; cd19 antigen; cd28 antigen; tumor necrosis factor; virus reactivation; cd22 antigen; interleukin 1; interleukin 18; phase 2 clinical trial (topic); phase 1 clinical trial (topic); interleukin 4 receptor; cytokine release syndrome; aplasia; tocilizumab; cd37 antigen; cellular therapy; cd123 antigen; human; receptor tyrosine kinase like orphan receptor; car t cells; durvalumab; tisagenlecleucel t; chimeric antigen receptor t-cell immunotherapy; axicabtagene ciloleucel |
| Journal Title: | Frontiers in Immunology |
| Volume: | 11 |
| ISSN: | 1664-3224 |
| Publisher: | Frontiers Media S.A. |
| Date Published: | 2020-05-12 |
| Start Page: | 888 |
| Language: | English |
| DOI: | 10.3389/fimmu.2020.00888 |
| PUBMED: | 32477359 |
| PROVIDER: | scopus |
| PMCID: | PMC7235422 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 July 2020 -- Source: Scopus |
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