CAR-T Cells Shoot for New Targets: Novel Approaches to Boost Adoptive Cell Therapy for B Cell-Derived Malignancies

Katsiaryna Marhelava; Marta Krawczyk; Malgorzata Firczuk; Klaudyna Fidyt

doi:10.3390/cells11111804

CAR-T Cells Shoot for New Targets: Novel Approaches to Boost Adoptive Cell Therapy for B Cell-Derived Malignancies

Cells. 2022 May 31;11(11):1804. doi: 10.3390/cells11111804.

Authors

Katsiaryna Marhelava¹, Marta Krawczyk^{1

2

3}, Malgorzata Firczuk^{1

2}, Klaudyna Fidyt¹

Affiliations

¹ Department of Immunology, Medical University of Warsaw, 02-097 Warsaw, Poland.
² Laboratory of Immunology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland.
³ Doctoral School of Translational Medicine, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland.

Abstract

Chimeric antigen receptor (CAR)-T cell therapy is undeniably a promising tool in combating various types of hematological malignancies. However, it is not yet optimal and a significant number of patients experience a lack of response or relapse after the treatment. Therapy improvement requires careful analysis of the occurring problems and a deeper understanding of the reasons that stand behind them. In this review, we summarize the recent knowledge about CAR-T products' clinical performance and discuss diversified approaches taken to improve the major shortcomings of this therapy. Especially, we prioritize the challenges faced by CD19 CAR-T cell-based treatment of B cell-derived malignancies and revise the latest insights about mechanisms mediating therapy resistance. Since the loss of CD19 is one of the major obstacles to the success of CAR-T cell therapy, we present antigens that could be alternatively used for the treatment of various types of B cell-derived cancers.

Keywords: B cell lymphoma; B-ALL; CAR-T cells; CD19 antigen; adoptive immunotherapy; resistance mechanism.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antigens, CD19
Cell- and Tissue-Based Therapy
Humans
Immunotherapy, Adoptive*
Leukemia, B-Cell* / therapy
Lymphoma, B-Cell* / therapy
Neoplasm Recurrence, Local
Receptors, Antigen, T-Cell*
Receptors, Chimeric Antigen*
T-Lymphocytes

Substances

Antigens, CD19
Receptors, Antigen, T-Cell
Receptors, Chimeric Antigen

Grants and funding

This work was supported by the National Centre for Research and Development within POLNOR program NOR/POLNOR/ALTERCAR/0056/2019 (PI: Magdalena Winiarska) and by the Ministry of Education and Science within “Regional Initiative of Excellence” in years 2019–2022, program 013/RID/2018/19, project budget 12,000,000 PLN (PI: Jakub Golab).