Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia

Quintarelli, Concetta; Sivori, Simona; Caruso, Simona; Carlomagno, Simona; Falco, Michela; Boffa, Iolanda; Orlando, Domenico; Guercio, Marika; Abbaszadeh, Zeinab; Sinibaldi, Matilde; Cecca, Stefano Di; Camera, Antonio; Cembrola, Biancamaria; Pitisci, Angela; Andreani, Marco; Vinti, Luciana; Gattari, S; Bufalo, Francesca Del; Algeri, Mattia; Pira, Giuseppina Li; Moseley, Annemarie; Angelis, Biagio De; Moretta, Alessandro; Locatelli, Franco

doi:10.1038/s41375-019-0613-7

Cited by 76 publications

(67 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, the secreted IL-15 is also capable of increasing the response of patients to CAR NK cell therapy. With the enhancement, the aphesis of NK cells from healthy adult donors and induced by cord blood stem cells was an efficient and inexpensive source of CAR NK cell therapy [132,133]. The CAR NK cells were successfully designed and tested in hematological malignancies and solid tumors in preclinical studies [134][135][136].…”

Section: The Sources Of T Cellsmentioning

confidence: 99%

Recent advances in CAR-T cell engineering

et al. 2020

View full text Add to dashboard Cite

Chimeric antigen receptor T (CAR-T) cell therapy is regarded as an effective solution for relapsed or refractory tumors, particularly for hematological malignancies. Although the initially approved anti-CD19 CART therapy has produced impressive outcomes, setbacks such as high relapse rates and resistance were experienced, driving the need to discover engineered CART cells that are more effective for therapeutic use. Innovations in the structure and manufacturing of CART cells have resulted in significant improvements in efficacy and persistence, particularly with the development of fourth-generation CART cells. Paired with an immune modifier, the use of fourthgeneration and next-generation CART cells will not be limited because of cytotoxic effects and will be an efficient tool for overcoming the tumor microenvironment. In this review, we summarize the recent transformations in the ectodomain, transmembrane domain, and endodomain of the CAR structure, which, together with innovative manufacturing technology and improved cell sources, improve the prospects for the future development of CART cell therapy.

show abstract

Section: The Sources Of T Cellsmentioning

confidence: 99%

Recent advances in CAR-T cell engineering

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The interest toward these cells in this setting depends on their specific characteristics. In addition to the CAR-specific target recognition, transduced NK cells retain the ability to recognize neoplastic cells through their innate receptors, thus reducing the risk of tumor escape (254). Since NK cells do not require HLA matching for target recognition, allogeneic NK cells do not cause GVHD.…”

Section: Car Nk Cellsmentioning

confidence: 99%

The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice

et al. 2020

View full text Add to dashboard Cite

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 Cerrano et al. CART Research and Clinical Practice 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.

show abstract

“…The development of efficient methods to genetically manipulate NK cells has been seen as a necessity to optimize their persistence in vivo, as well as their location and cytotoxicity against the tumor cells after the adoptive transfer [133][134][135]. Finally, clinical trials are being conducted in which NK cells expressing CAR (chimeric antigen receptor) are administered to patients, after having proven their efficacy in preclinical models [134][135][136][137][138].…”

Section: Nk Cells In Cancer Immunotherapymentioning

confidence: 99%

NK Cell-Based Immunotherapy in Renal Cell Carcinoma

Terrén

Orrantia

Mikelez-Alonso

et al. 2020

Cancers

View full text Add to dashboard Cite

Natural killer (NK) cells are cytotoxic lymphocytes that are able to kill tumor cells without prior sensitization. It has been shown that NK cells play a pivotal role in a variety of cancers, highlighting their relevance in tumor immunosurveillance. NK cell infiltration has been reported in renal cell carcinoma (RCC), the most frequent kidney cancer in adults, and their presence has been associated with patients’ survival. However, the role of NK cells in this disease is not yet fully understood. In this review, we summarize the biology of NK cells and the mechanisms through which they are able to recognize and kill tumor cells. Furthermore, we discuss the role that NK cells play in renal cell carcinoma, and review current strategies that are being used to boost and exploit their cytotoxic capabilities.

show abstract

Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia

Cited by 76 publications

References 49 publications

Recent advances in CAR-T cell engineering

Recent advances in CAR-T cell engineering

The Advent of CAR T-Cell Therapy for Lymphoproliferative Neoplasms: Integrating Research Into Clinical Practice

NK Cell-Based Immunotherapy in Renal Cell Carcinoma

Contact Info

Product

Resources

About