Activation of T Lymphocytes with Anti-PDL1-BiTE in the Presence of Adipose-Derived Mesenchymal Stem Cells (ASCs).
Background. Due to their ability to recruit immune cells to kill tumor cells directly, bispecific T cell engager antibodies (BiTE) hold great potential in T cell redirecting therapies. BiTE is able to activate T cells through CD3 and target them to tumor-expressed antigens. However, there are many c...
| Publicado en: | BioMed Research International pp. 1 - 12 |
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| Autores principales: | , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
6/7/2023
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=164183762&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 164183762 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 6/7/2023 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 164183762 164183762 164183762 10.1155/2023/7692726 164183762 ppf: 1 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Activation of T Lymphocytes with Anti-PDL1-BiTE in the Presence of Adipose-Derived Mesenchymal Stem Cells (ASCs). aug: au: Moeinzadeh, Leila Ramezani, Amin Mehdipour, Fereshteh Yazdanpanah-Samani, Mahsa Razmkhah, Mahboobeh affil: Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran sug: subj: Antibodies, Monoclonal Pharmacodynamics Cell Proliferation Drug Effects T Lymphocytes Drug Effects Mesenchymal Stem Cells Immunotherapy Methods Human Programmed Cell Death Ligand 1 Drug Effects Flow Cytometry Recombinant Proteins Cell Line, Tumor Enzyme-Linked Immunosorbent Assay Blotting, Western Post Hoc Analysis Data Analysis Software One-Way Analysis of Variance Descriptive Statistics Funding Source ab: Background. Due to their ability to recruit immune cells to kill tumor cells directly, bispecific T cell engager antibodies (BiTE) hold great potential in T cell redirecting therapies. BiTE is able to activate T cells through CD3 and target them to tumor-expressed antigens. However, there are many components in the tumor microenvironment (TME) such as mesenchymal stem cells (MSCs) that may interfere with BiTE function. Herein, we designed an anti-PDL1-BiTE that targets programmed death ligand 1 (PDL1) and CD3 and investigated its effect on PDL1pos cancer cells in the presence or absence of adipose-derived MSCs (ASCs). Method. Our anti-PDL1-BiTE comprises of VL and VH chains of anti-CD3 monoclonal antibody (mAb) linked to the VL and VH chains of anti-PDL1 mAb, which simultaneously bind to the CD3ε subunit on T cells and PDL1 on tumor cells. Flow cytometry was employed to assess the strength of binding of anti-PDL1-BiTE to tumor cells and T cells. Cytotoxicity, proliferation, and activation of peripheral blood lymphocyte (PBLs) were evaluated by CFSE assay and flow cytometry after using anti-PDL1-BiTE in the presence or absence of ASCs and their conditioned media (C.M.). Results. Anti-PDL1-BiTE had the ability to induce selective lysis of PDL1pos U251-MG cancer cells while PDL1neg cells were not affected. Also, anti-PDL1-BiTE significantly stimulated peripheral blood lymphocyte (PBL) proliferation and CD69 expression. ASCs/C.M. did not show a significant effect on the biological activity of anti-PDL1-BiTE. Conclusion. Overall, anti-PDL1-BiTE selectively depletes PDL1pos cells and represents a new immunotherapeutic approach. It would increase the accumulation of T cells and can improve the prognosis of PDL1pos cancers in spite of the immunomodulatory effects of ASCs and C.M. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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