scholarly journals Potential Role of CD47-Directed Bispecific Antibodies in Cancer Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Yang ◽  
Zheng Yang ◽  
Yun Yang
Keyword(s):  
Cancer Immunotherapy ◽  
Potential Role ◽  
Bispecific Antibody ◽  
Lymphoblastic Leukemia ◽  
Bispecific Antibodies ◽  
The Novel ◽  
Mechanisms Of Resistance ◽  
Immunological Therapy ◽  
Novel Targets

The prosperity of immunological therapy for cancer has aroused enormous passion for exploiting the novel targets of cancer immunotherapy. After the approval of blinatumomab, a bispecific antibody (bsAb) targeting on CD19 for acute lymphoblastic leukemia, a few of CD47-targeted bsAbs for cancer immunotherapy, are currently in clinical research. In our review of CD47-targeted bsAbs, we described the fundamental of bsAbs. Then, we summarized the information of four undergoing phase I researches, reviewed the main toxicities relevant to CD47-targeted bsAb immunological therapy of on-target cytotoxicity to healthy cells and a remarkable antigen-sink. Finally, we described possible mechanisms of resistance to CD47-targeted bsAb therapy. More clinical researches are supposed to adequately confirm its security and efficacy in clinical practice.

scholarly journals Genome-wide transcriptome analysis identifies alternative splicing regulatory network and key splicing factors in mouse and human psoriasis

2018 ◽  
Author(s):  
Jin Li ◽  
Peng Yu
Keyword(s):  
Alternative Splicing ◽  
Computational Analysis ◽  
Potential Role ◽  
Exon Skipping ◽  
Chronic Inflammatory Disease ◽  
Splicing Factors ◽  
The Novel ◽  
Rna Seq ◽  
Genome Wide

AbstractPsoriasis is a chronic inflammatory disease that affects the skin, nails, and joints. For understanding the mechanism of psoriasis, though, alternative splicing analysis has received relatively little attention in the field. Here, we developed and applied several computational analysis methods to study psoriasis. Using psoriasis mouse and human datasets, our differential alternative splicing analyses detected hundreds of differential alternative splicing changes. Our analysis of conservation revealed many exon-skipping events conserved between mice and humans. In addition, our splicing signature comparison analysis using the psoriasis datasets and our curated splicing factor perturbation RNA-Seq database, SFMetaDB, identified nine candidate splicing factors that may be important in regulating splicing in the psoriasis mouse model dataset. Three of the nine splicing factors were confirmed upon analyzing the human data. Our computational methods have generated predictions for the potential role of splicing in psoriasis. Future experiments on the novel candidates predicted by our computational analysis are expected to provide a better understanding of the molecular mechanism of psoriasis and to pave the way for new therapeutic treatments.

scholarly journals Role of Bispecific antibody for Multiple Myeloma; A literature Review

2021 ◽  
pp. 1-4
Author(s):  
Madeeha Subhan Waleed ◽  
Keyword(s):  
Multiple Myeloma ◽  
Binding Sites ◽  
Bispecific Antibody ◽  
Organ Damage ◽  
Bispecific Antibodies ◽  
Efficacy And Safety ◽  
Potential Benefits ◽  
Wide Group ◽  
New Treatments

Multiple myeloma (MM), as defined by a clonal plasma cell proliferation, manifests as end organ damage caused by the abnormally high monoclonal paraprotein.In this article, we have reviewed the potential benefits of Bispecific antibodies (BsAbs) in MM patients. In addition, new BsAbs developments and clinical trials for various MM targets are discussed in detail. Bispecific antibodies are the types of antibodies that have two different antigen binding sites in one molecule. There are 100 different classes of BsAb and all these can be divided into 2 main categories based on their fragments and both categories are under trials for MM.Despite some studies showing adverse effects development of these new treatments is going to greatly contribute to improve outcomes for a wide group of patients which also requires further clinical studies to be conducted with focus on demonstration of efficacy and safety profile.

scholarly journals Detection of single nucleotide polymorphisms at major prolificacy genes in the Mehraban sheep and association with litter size

2018 ◽  
Vol 18 (3) ◽  
pp. 685-698 ◽  
Author(s):  
Reza Talebi ◽  
Ahmad Ahmadi ◽  
Fazlollah Afraz ◽  
Julien Sarry ◽  
Florent Woloszyn ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Litter Size ◽  
Potential Role ◽  
Chromosome 6 ◽  
The Novel ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hardy Weinberg Equilibrium ◽  
Gdf9 Gene

Abstract The present study aimed to investigate the presence of polymorphisms at four known genes controlling ovine prolificacy i.e. BMP15, GDF9, BMPR1B and B4GALNT2 in a sample of 115 Iranian Mehraban ewes and their association with litter size (LS) and lambs’ birth weight (BW) traits. Using Sanger sequencing of exons and polymorphism specific genotyping, ten SNPs (Single Nucleotide Polymorphisms) were observed in only two genes, GDF9 and BMPR1B. Seven SNPs were found in the GDF9 gene on the chromosome 5. Among them, six were already described in the coding sequence, and a new one (g.41840985C>T) was found in the 3’UTR. In the BMPR1B gene on the chromosome 6, three novel SNPs were detected in the exon 7 (g.29382184G>A; g.29382337G>A and g.29382340G>A). Allelic frequencies were established for six SNPs among the ten identified and they were in Hardy-Weinberg equilibrium. A significant association was found between the novel SNPs found in the exon 7 of BMPR1B and LS. Present results indicate the potential role of the BMPR1B locus in controlling prolificacy of Mehraban sheep and provide genetic markers for further exploitation in selection to improve reproductive efficiency.

scholarly journals Facile Generation of Potent Bispecific Fab via Sortase A and Click Chemistry for Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4540
Author(s):  
Xuefei Bai ◽  
Wenhui Liu ◽  
Shijie Jin ◽  
Wenbin Zhao ◽  
Yingchun Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Click Chemistry ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Bispecific Antibody ◽  
Bispecific Antibodies ◽  
Great Promise ◽  
Sortase A ◽  
Superior Efficacy ◽  
Mouse Xenograft Model

Bispecific antibodies (BsAbs) for T cell engagement have shown great promise in cancer immunotherapy, and their clinical applications have been proven in treating hematological malignance. Bispecific antibody binding fragment (BiFab) represents a promising platform for generating non-Fc bispecific antibodies. However, the generation of BiFab is still challenging, especially by means of chemical conjugation. More conjugation strategies, e.g., enzymatic conjugation and modular BiFab preparation, are needed to improve the robustness and flexibility of BiFab preparation. We successfully used chemo-enzymatic conjugation approach to generate bispecific antibody (i.e., BiFab) with Fabs from full-length antibodies. Paired click handles (e.g., N3 and DBCO) was introduced to the C-terminal LPETG tag of Fabs via sortase A mediated transpeptidation, followed by site-specific conjugation between two click handle-modified Fabs for BiFab generation. Both BiFabCD20/CD3 (EC50 = 0.26 ng/mL) and BiFabHer2/CD3 exhibited superior efficacy in mediating T cells, from either PBMC or ATC, to kill target tumor cell lines while spared antigen-negative tumor cells in vitro. The BiFabCD20/CD3 also efficiently inhibited CD20-positive tumor growth in mouse xenograft model. We have established a facile sortase A-mediated click handle installation to generate homogeneous and functional BiFabs. The exemplary BiFabs against different targets showed superior efficacy in redirecting and activating T cells to specifically kill target tumor cells, demonstrating the robustness of sortase A-mediated “bio-click” chemistry in generating various potent BiFabs. This approach also holds promise for further efficient construction of a Fab derivative library for personalized tumor immunotherapy in the future.

scholarly journals The Clinical Significance and Biological Function of DPEP1 in B-cell Acute Lymphoblastic Leukemia

2019 ◽  
Author(s):  
Jia-Min Zhang ◽  
Yan Xu ◽  
Robert Peter Gale ◽  
Li-Xin Wu ◽  
Jing Zhang ◽  
...  
Keyword(s):  
B Cell ◽  
Potential Role ◽  
Biological Function ◽  
Lymphoblastic Leukemia ◽  
Therapy Outcomes ◽  
Transcript Levels ◽  
Biological Basis ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Therapy Target

AbstractDehydropeptidase-1 (DPEP1) is a zinc-dependent metalloproteinase abnormally expressed in many cancers. However, its potential role in adults with B-cell acute lymphoblastic leukaemia (ALL) is unknown.We found that in adults with common-B-cell ALL high DPEP1 transcript levels at diagnosis was independently-associated with an increased CIR and worse RFS compared with subjects with low transcript levels. We show an increased proliferation and pro-survival role of DPEP1 in B-cell ALL cells via regulation of phosphCREB and p53 which may be the biological basis of the clinical correlation we report. Our data implicate DPEP1 expression in the biology of common B-cell ALL in adults. We report clinical correlates and provide a potential biological basis for these correlations. If confirmed, analyzing DPEP1 transcript levels at diagnosis could help predict therapy-outcomes. Moreover, regulation of DPEP1 expression could be a therapy target in B-cell ALL.

Muscle Rad expression and human metabolism: potential role of the novel Ras-related GTPase in energy expenditure and body composition

Diabetes ◽  
1997 ◽  
Vol 46 (3) ◽  
pp. 444-450 ◽  
Author(s):  
W. T. Garvey ◽  
L. Maianu ◽  
A. Kennedy ◽  
P. Wallace ◽  
E. Ganaway ◽  
...  
Keyword(s):  
Body Composition ◽  
Energy Expenditure ◽  
Potential Role ◽  
The Novel ◽  
Human Metabolism

scholarly journals Tackling Resistance to Cancer Immunotherapy: What Do We Know?

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4096
Author(s):  
Soehartati A. Gondhowiardjo ◽  
Handoko ◽  
Vito Filbert Jayalie ◽  
Riyan Apriantoni ◽  
Andreas Ronald Barata ◽  
...  
Keyword(s):  
Immune System ◽  
Cancer Treatment ◽  
Cancer Immunotherapy ◽  
Small Subset ◽  
Mechanisms Of Resistance ◽  
Conventional Surgery ◽  
Cancer Treatments ◽  
Conventional Cancer Treatment ◽  
Combinatorial Treatment

Cancer treatment has evolved tremendously in the last few decades. Immunotherapy has been considered to be the forth pillar in cancer treatment in addition to conventional surgery, radiotherapy, and chemotherapy. Though immunotherapy has resulted in impressive response, it is generally limited to a small subset of patients. Understanding the mechanisms of resistance toward cancer immunotherapy may shed new light to counter that resistance. In this review, we highlighted and summarized two major hurdles (recognition and attack) of cancer elimination by the immune system. The mechanisms of failure of some available immunotherapy strategies were also described. Moreover, the significance role of immune compartment for various established cancer treatments were also elucidated in this review. Then, the mechanisms of combinatorial treatment of various conventional cancer treatment with immunotherapy were discussed. Finally, a strategy to improve immune cancer killing by characterizing cancer immune landscape, then devising treatment based on that cancer immune landscape was put forward.

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