Background: Cytokine-induced killer cells (CIKs) adoptive cell transfer (ACT) is a common malignant tumor treatment method. Interleukin-2 (IL-2) is one of the essential cytokines for CIKs cultures. In different phase of CIKs (quiescent and exponential growth), due to different active states and IL-2R expression of the CIKs surface, different doses of IL-2 are required. However, most studies, only addressed the effects of IL-2 concentrations on the function of CIKs, and the differences between varied administration methods of IL-2 have not been explored.
Methods: This study established a novel sequential administration methods for IL-2. Different concentrations of IL-2 were added during different CIKs induction phases. Then, the proliferation ability of CIKs was evaluated using cell proliferation curves. The immune phenotype was analyzed by flow cytometry (FCM), and IFN-γ secretion ability and cytotoxicity were detected using enzyme-linked immunosorbent assay (ELISA) kits and cell counting kit-8, respectively. Multiple comparisons were conducted between each group to compare the function of CIKs in 12 experimental groups.
Results: As the IL-2 concentration increased, the number of CIKs continued to increase in each group, but the function of CIKs was not positively related to its number: CD3+ CD56+ subpopulation ratio, INF-γ secretion ability, and cytotoxicity showed irregular changes. During the quiescent and exponential growth phases, adding 300 and 1,000 U/mL IL-2 respectively achieved powerful CIKs (cell numbers of day 16: (384.37±2.05)×10/mL, proliferation: 128.12, CD3+ CD56+ subpopulation ratio: 40.9%, INF-γ secretion ability: 542 pg/mL, cytotoxicity: 40:1, 74.22).
Conclusions: Different concentrations of IL-2 had a greater influence on the biological function of CIKs in different growth phases, and it is better to add IL-2 sequentially during the quiescent and exponential growth phases of CIKs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799159 | PMC |
| http://dx.doi.org/10.21037/tcr-21-556 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Rooting for order: How CIKs keep lateral growth in check.
Plant Physiol
December 2024
Assistant Features Editor, Plant Physiology, American Society of Plant Biologists.
CLAVATA3 INSENSITIVE RECEPTOR KINASEs regulate lateral root initiation and spacing in Arabidopsis.
Plant Physiol
December 2024
Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
Article Synopsis
- The study investigates how CLAVATA3 INSENSITIVE RECEPTOR KINASEs (CIKs) affect lateral root (LR) development in plants, specifically Arabidopsis, revealing their importance in LR initiation and spacing alongside RECEPTOR-LIKE KINASE 7 (RLK7).
- CIK mutants displayed an increase in LR formation due to improper spacing and reduced sensitivity to the TOLS2 peptide, suggesting a disruption in the signaling pathway between TOLS2 and RLK7.
- The research identifies a signaling cascade involving MKK4/5 and the transcription factor PUCHI that helps CIKs and RLK7 coordinate LR development in response to auxin concentration in specific root
Functional Activity of Cytokine-Induced Killer Cells Enhanced by CAR-CD19 Modification or by Soluble Bispecific Antibody Blinatumomab.
Antibodies (Basel)
August 2024
Center of Cellular Therapy "G. Lanzani", Division of Hematology, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy.
Strategies to increase the anti-tumor efficacy of cytokine-induced killer cells (CIKs) include genetic modification with chimeric antigen receptors (CARs) or the addition of soluble T-cell engaging bispecific antibodies (BsAbs). Here, CIKs were modified using a transposon system integrating two distinct anti-CD19 CARs (CAR-MNZ and CAR-BG2) or combined with soluble CD3xCD19 BsAb blinatumomab (CIK + Blina). CAR-MNZ bearing the CD28-OX40-CD3ζ signaling modules, and CAR-BG2, designed on the Tisagenlecleucel CAR sequence (Kymriah), carrying the 4-1BB and CD3ζ signaling elements, were employed.
View Article and Find Full Text PDFCytokine-induced killer cells: new insights for therapy of hematologic malignancies.
Stem Cell Res Ther
August 2024
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Background: Cytokine-induced killer (CIK) cells are a novel subgroup of immune effectors, classified as one of the modified T cell-mediated arms for immunotherapy. These cells exert MHC-unrestricted cytotoxicity against both hematological and solid malignancies with low incidence of treatment-related severe complications. This study reviews the application of CIK cells in treating cases with hematologic malignancies.
View Article and Find Full Text PDFThe IL-17 pathway intertwines with neurotrophin and TLR/IL-1R pathways since its domain shuffling origin.
Proc Natl Acad Sci U S A
May 2024
State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
The IL-17 pathway displays remarkably diverse functional modes between different subphyla, classes, and even orders, yet its driving factors remains elusive. Here, we demonstrate that the IL-17 pathway originated through domain shuffling between a Toll-like receptor (TLR)/IL-1R pathway and a neurotrophin-RTK (receptor-tyrosine-kinase) pathway (a Trunk-Torso pathway). Unlike other new pathways that evolve independently, the IL-17 pathway remains intertwined with its donor pathways throughout later evolution.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!