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Review
. 2024 May 25;25(11):5769.
doi: 10.3390/ijms25115769.

Granulocyte Colony Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells: An Alternative Cellular Source for Chimeric Antigen Receptor Therapy

Affiliations
Review

Granulocyte Colony Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells: An Alternative Cellular Source for Chimeric Antigen Receptor Therapy

Antonio Ballesteros-Ribelles et al. Int J Mol Sci. .

Abstract

Lymphocyte collection by apheresis for CAR-T production usually does not include blood mobilized using granulocyte colony stimulating factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinics, makes it necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent works that experimentally verify the role and functionality of T and NK lymphocytes and the generation of CAR-T from apheresis after G-CSF mobilization. As discussed, T cells do not vary significantly in their phenotype, the ratio of CD4+ and CD8+ remains constant, and the different sub-populations remain stable. In addition, the expansion and proliferation rates are invariant regardless of mobilization with G-CSF as well as the secretion of proinflammatory cytokines and the cytotoxic ability. Therefore, cells mobilized before apheresis are postulated as a new alternative source of T cells for adoptive therapies that will serve to alleviate high demand, increase availability, and take advantage of the substantial number of existing cryopreserved products.

Keywords: CAR-NK; CAR-T; G-CSF; mobilization.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Generations of CAR cells: First-generation CAR cells, equipped with an extracellular antigen-recognizing domain combined with intracellular CD3z accounting for signal transduction. Second-generation CAR cells, equipped with an extracellular antigen-recognizing domain combined with two intracellular domains: CD3z and an additional costimulatory domain like CD28 or 4-1BB. Third-generation CAR cells, equipped with an extracellular antigen-recognizing domain combined with three intracellular domains: CD3z and two additional costimulatory domains. Fourth-generation CAR cells, a diversified group of CAR constructs like cytokine-expressing CAR cells. Created with BioRender.com.
Figure 2
Figure 2
On the left side, cells have not been exposed to G-CSF; therefore, osteoblasts and endothelial cells show on their surface a high expression of cell-adhesion-related molecules, such as SDF-1, VCAM- 1, or kitL. On the right side, cells have been exposed to G-CSF, a molecule recognized by the G-CSFR receptor. This causes neutrophils to release protease enzymes that accumulate in the BM and degrade molecules related to cell adhesion. Furthermore, both the secretion of adrenaline by sympathetic neurons and the secretion of certain factors by macrophages promote a reduction in SDF-1 expression, which leads to the disjunction and mobilization of HSPC cells from the bone marrow. Created with BioRender.com.
Figure 3
Figure 3
Illustration of the clinical aspects of the apheresis process for the collection of HSCs through the therapeutic administration of G-CSF, showing the process of mobilization of CD34+ cells from the bone marrow to the peripheral blood for subsequent collection. Created with BioRender.com.

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