Development of fluorescence-labeled antibody for immune checkpoint inhibitor using engineered probiotics

Namai, Fu; Sumiya, Shunsuke; Nomura, N.; Sato, Takashi; Shimosato, Takeshi

doi:10.1186/s13568-023-01509-y

Cited by 2 publications

(1 citation statement)

References 35 publications

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“…Emerging evidence indicates that, for binding of anti-PD-L1 monoclonal antibodies, the VH is essential, rather than VL chains [ 35 ], suggesting that the HA tag at the N-terminus of VH may negatively impact the functionality of the expressed fragment. However, in contrast to this theory, others have constructed a functional anti-PD-L1 scFv with the GFP-encoding sequence at the N-terminus of the VH [ 64 ]. Thus, we examined both strategies by constructing two anti-PD-L1 scFv configurations: one with the HA tag placed at the N-terminus of the VH chain (anti-PD-L1-N) and the other with the HA tag positioned outside the scFv, at the N-terminus of SAG1 (anti-PD-L1-C).…”

Section: Discussionmentioning

confidence: 99%

Specific Cell Targeting by Toxoplasma gondii Displaying Functional Single-Chain Variable Fragment as a Novel Strategy; A Proof of Principle

Aljieli,

Rivière,

Lantier

et al. 2024

Cells

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Toxoplasma gondii holds significant therapeutic potential; however, its nonspecific invasiveness results in off-target effects. The purpose of this study is to evaluate whether T. gondii specificity can be improved by surface display of scFv directed against dendritic cells’ endocytic receptor, DEC205, and immune checkpoint PD-L1. Anti-DEC205 scFv was anchored to the T. gondii surface either directly via glycosylphosphatidylinositol (GPI) or by fusion with the SAG1 protein. Both constructs were successfully expressed, but the binding results suggested that the anti-DEC-SAG1 scFv had more reliable functionality towards recombinant DEC protein and DEC205-expressing MutuDC cells. Two anti-PD-L1 scFv constructs were developed that differed in the localization of the HA tag. Both constructs were adequately expressed, but the localization of the HA tag determined the functionality by binding to PD-L1 protein. Co-incubation of T. gondii displaying anti-PD-L1 scFv with tumor cells expressing/displaying different levels of PD-L1 showed strong binding depending on the level of available biomarker. Neutralization assays confirmed that binding was due to the specific interaction between anti-PD-L1 scFv and its ligand. A mixed-cell assay showed that T. gondii expressing anti-PD-L1 scFv predominately targets the PD-L1-positive cells, with negligible off-target binding. The recombinant RH-PD-L1-C strain showed increased killing ability on PD-L1+ tumor cell lines compared to the parental strain. Moreover, a co-culture assay of target tumor cells and effector CD8+ T cells showed that our model could inhibit PD1/PD-L1 interaction and potentiate T-cell immune response. These findings highlight surface display of antibody fragments as a promising strategy of targeting replicative T. gondii strains while minimizing nonspecific binding.

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Section: Discussionmentioning

confidence: 99%

Specific Cell Targeting by Toxoplasma gondii Displaying Functional Single-Chain Variable Fragment as a Novel Strategy; A Proof of Principle

Aljieli,

Rivière,

Lantier

et al. 2024

Cells

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Surface Engineering on Bacteria for Tumor Immunotherapy: Strategies and Perspectives

Fu,

He,

et al. 2024

Adv Funct Materials

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Bacteria have garnered significant attention in tumor immunotherapy recently years, owing to their immune‐activating properties, ease of genetic manipulation, and colonization abilities. In order to further enhance the safety, efficacy, and clinical translation potential of bacterial therapy, and to endow bacteria with additional functions, modifications or engineering of bacterial surfaces have emerged as a current research hotspot. This review systematically summarizes the primary methods and strategies for bacterial surface modification and engineering, including chemical alteration, physical modification, and bio‐modification. Subsequently, it is delve into the roles of these techniques in enhancing bacterial tumor immunotherapy, such as improving immunotherapeutic efficacy and reducing toxic side effects, and elucidate the underlying mechanisms. Finally, the current challenges faced in this field are deeply explored, and potential solutions for the future are presented. This work offers a comprehensive overview of the advancements in the new generation of bacterial surface modification techniques and their implications in bacterial‐based tumor immunotherapy.

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Development of fluorescence-labeled antibody for immune checkpoint inhibitor using engineered probiotics

Cited by 2 publications

References 35 publications

Specific Cell Targeting by Toxoplasma gondii Displaying Functional Single-Chain Variable Fragment as a Novel Strategy; A Proof of Principle

Specific Cell Targeting by Toxoplasma gondii Displaying Functional Single-Chain Variable Fragment as a Novel Strategy; A Proof of Principle

Surface Engineering on Bacteria for Tumor Immunotherapy: Strategies and Perspectives

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