Antibody and antibody fragments for cancer immunotherapy

Chen, Weizhi; Yang, Yuan; Jiang, Xiqun

doi:10.1016/j.jconrel.2020.08.021

Cited by 84 publications

(74 citation statements)

References 136 publications

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“…Conventional antigen-specific B-2 cells play an important role in the later course of infection by producing antibodies that opsonize pathogens [60] and bind infected cells, which de novo express pathogen-specific proteins on their surface, resulting in antibodydependent cellular cytotoxicity, cell phagocytosis and complement-dependent cytotoxicity [61]. The same mechanisms are exploited by numerous clinically applied monoclonal antibodies designed to label malignant cells [62]. We exploited the intrinsic, complementmediated binding of FeO-DEX to splenic B cells to shift T helper cell type 2 (Th2)-biased humoral responses towards Th1 [7] using CpG ODN as an adjuvant [63].…”

Section: Discussionmentioning

confidence: 99%

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

Bednarczyk

Medina‐Montano

Fittler

et al. 2021

IJMS

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The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.

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Section: Discussionmentioning

confidence: 99%

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

Bednarczyk

Medina‐Montano

Fittler

et al. 2021

IJMS

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“…One of the limitations that an immunotoxin with an antibody fragment such as scFv is that it lacks the Fc domain of IgG. The Fc domain is responsible for several in vivo functions of a full-length antibody [ 49 ]. First, it mediates strong antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cell phagocytosis (ADCP) by binding to Fc gamma receptors (FcγRs) of immune cells.…”

Section: Discussionmentioning

confidence: 99%

Soluble Cytoplasmic Expression and Purification of Immunotoxin HER2(scFv)-PE24B as a Maltose Binding Protein Fusion

Park

Nguyen

et al. 2021

IJMS

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Human epidermal growth factor receptor 2 (HER-2) is overexpressed in many malignant tumors. The anti-HER2 antibody trastuzumab has been approved for treating HER2-positive early and metastatic breast cancers. Pseudomonas exotoxin A (PE), a bacterial toxin of Pseudomonas aeruginosa, consists of an A-domain with enzymatic activity and a B-domain with cell binding activity. Recombinant immunotoxins comprising the HER2(scFv) single-chain Fv from trastuzumab and the PE24B catalytic fragment of PE display promising cytotoxic effects, but immunotoxins are typically insoluble when expressed in the cytoplasm of Escherichia coli, and thus they require solubilization and refolding. Herein, a recombinant immunotoxin gene was fused with maltose binding protein (MBP) and overexpressed in a soluble form in E. coli. Removal of the MBP yielded stable HER2(scFv)-PE24B at 91% purity; 0.25 mg of pure HER2(scFv)-PE24B was obtained from a 500 mL flask culture. Purified HER2(scFv)-PE24B was tested against four breast cancer cell lines differing in their surface HER2 level. The immunotoxin showed stronger cytotoxicity than HER2(scFv) or PE24B alone. The IC50 values for HER2(scFv)-PE24B were 28.1 ± 2.5 pM (n = 9) and 19 ± 1.4 pM (n = 9) for high HER2-positive cell lines SKBR3 and BT-474, respectively, but its cytotoxicity was lower against MDA-MB-231 and MCF7. Thus, fusion with MBP can facilitate the soluble expression and purification of scFv immunotoxins.

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“…Although polyclonal antibodies can be produced in a shorter timeframe, the binding sites of the polyclonal antibodies to the antigen are different, since each clonal antibody has an affinity to different epitopes of the same antigen [ 22 ]. Thus, monoclonal antibodies (mAbs) with an affinity to the same epitopes of the antigen are strongly preferred in therapeutic applications and immunotherapy [ 23 , 24 , 25 ].…”

Section: Conventional and Advanced Analytical Technologiesmentioning

confidence: 99%

Recent Advances in Conventional Methods and Electrochemical Aptasensors for Mycotoxin Detection

Ong

Pike

Tan

2021

Foods

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The presence of mycotoxins in foodstuffs and feedstuffs is a serious concern for human health. The detection of mycotoxins is therefore necessary as a preventive action to avoid the harmful contamination of foodstuffs and animal feed. In comparison with the considerable expense of treating contaminated foodstuffs, early detection is a cost-effective way to ensure food safety. The high affinity of bio-recognition molecules to mycotoxins has led to the development of affinity columns for sample pre-treatment and the development of biosensors for the quantitative analysis of mycotoxins. Aptamers are a very attractive class of biological receptors that are currently in great demand for the development of new biosensors. In this review, the improvement in the materials and methodology, and the working principles and performance of both conventional and recently developed methods are discussed. The key features and applications of the fundamental recognition elements, such as antibodies and aptamers are addressed. Recent advances in aptasensors that are based on different electrochemical (EC) transducers are reviewed in detail, especially from the perspective of the diagnostic mechanism; in addition, a brief introduction of some commercially available mycotoxin detection kits is provided.

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Antibody and antibody fragments for cancer immunotherapy

Cited by 84 publications

References 136 publications

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

Soluble Cytoplasmic Expression and Purification of Immunotoxin HER2(scFv)-PE24B as a Maltose Binding Protein Fusion

Recent Advances in Conventional Methods and Electrochemical Aptasensors for Mycotoxin Detection

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