uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Approaches to augment CAR T-cell therapy by targeting the apoptotic machinery
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. (Angelica Loskog)
2016 (English)In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 44, no 2, 371-376 p.Article, review/survey (Refereed) Published
Abstract [en]

Chimaeric antigen receptor (CAR) T-cells have shown impressive results in patients with B-cell leukaemia. Yet, in patients with lymphoma durable responses are still rare and heavy preconditioning required. Apoptosis resistance is considered a hallmark of cancer, often conveyed by a halted apoptosis signalling. Tumours regularly skew the balance of the components of the apoptotic machinery either through up-regulating antiapoptotic proteins or silencing pro-apoptotic ones. Malignant B-cells frequently up-regulate anti-apoptotic B-cell lymphoma 2 (Bcl-2) family proteins leading to therapy resistance. CAR T-cells kill tumour cells via apoptosis induction and their efficacy may be affected by the level of Bcl-2 family proteins. Hence, there is an interesting possibility to increase the effect of CAR T-cell therapy by combining it with apoptosis inhibitor blockade agents. Compounds that inhibit Bcl-2, B-cell lymphoma extra large (Bcl-xL) and Bcl-2-like protein 2 (Bcl-w), can restore execution of apoptosis in tumour cells or sensitize them to other apoptosis-dependent treatments. Hence, there is a great interest to combine such agents with CAR T-cell therapy to potentiate the effect of CAR T-cell killing. This review will focus on the potential of targeting the apoptotic machinery to sensitize tumour cells to CAR T-cell killing.

Place, publisher, year, edition, pages
2016. Vol. 44, no 2, 371-376 p.
Keyword [en]
ABT-737; B-cell lymphoma 2 (Bcl-2) family proteins; chimaeric antigen receptor (CAR) T-cells; inhibitor of apoptosis protein (IAP); Navitoclax
National Category
URN: urn:nbn:se:uu:diva-290391DOI: 10.1042/BST20150253ISI: 000377518000007PubMedID: 27068942OAI: oai:DiVA.org:uu-290391DiVA: diva2:925105
Chimeric Antigen Receptor Therapy in Haematology and Oncology: Current Successes and Challenges: Held at Charles Darwin House, London, U.K., 19–20 October 2015
Swedish Childhood Cancer Foundation, PROJ08/028Swedish Cancer Society, CAN 2008/936Swedish Research Council, K2008-64P-20744-01-4AFA InsuranceÅke Wiberg FoundationMagnus Bergvall Foundation
Available from: 2016-04-29 Created: 2016-04-29 Last updated: 2016-07-22Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Karlsson, Hannah
By organisation
Clinical Immunology
In the same journal
Biochemical Society Transactions

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 95 hits
ReferencesLink to record
Permanent link

Direct link