Biomolecular Engineering of Antidehydroepiandrosterone Antibodies: A New Perspective in Cancer Diagnosis and Treatment Using Single-Chain Antibody Variable Fragment

Fogaça, Rafaela Lenzi; Alvarenga, Larissa M.; Woiski, Thiago Demetrius; Becker-Finco, Alessandra; Teixeira, Kádima Nayara; Silva, Sabrina K.; Moraes, Wanderlei de; Noronha, Lúcia de; Noiray, Magali; Figueiredo, Bonald C.; Billiald, Philippe; Moura, Juliana de

doi:10.2217/nnm-2018-0230

Cited by 7 publications

(4 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Antibodies against classic biomarkers have been studied, and are still being analyzed in terms of biodistribution, their ability to penetrate tissue, toxicity, and efficient clearance. Some examples include scFvs directed against chondroitin sulfate (CS, abundant in the extracellular matrix in ovarian cancer) [ 94 ], CD24 (overexpressed in several tumors and in cancerous stem cells) [ 95 ], oncoprotein E6, expressed continuously in carcinomas associated with human papilloma virus type 16 (HPV 16) [ 96 ], gastrin receptor (CCK2R, playing a key role in the trigger and development of cancer) [ 97 ], dehydroepiandrosterone (DHEA, adrenocortical carcinoma marker) [ 98 ], against cancer cells overexpressing EGFR (epidermal growth factor receptor) [ 99 ], MCF-7 breast cancer cells [ 100 , 101 ], and SUM159 (breast cancer stem cells) [ 102 ]. They have all shown promising results.…”

Section: Applications Of Scfvsmentioning

confidence: 99%

Single-Chain Fragment Variable: Recent Progress in Cancer Diagnosis and Therapy

Muñoz-López

Ribas‐Aparicio

Becerra-Báez

et al. 2022

Cancers

View full text Add to dashboard Cite

Cancer remains a public health problem worldwide. Although conventional therapies have led to some excellent outcomes, some patients fail to respond to treatment, they have few therapeutic alternatives and a poor survival prognosis. Several strategies have been proposed to overcome this issue. The most recent approach is immunotherapy, particularly the use of recombinant antibodies and their derivatives, such as the single-chain fragment variable (scFv) containing the complete antigen-binding domains of a whole antibody that successfully targets tumor cells. This review describes the recent progress made with scFvs as a cancer diagnostic and therapeutic tool, with an emphasis on preclinical approaches and their potential use in clinical trials.

show abstract

Section: Applications Of Scfvsmentioning

confidence: 99%

Single-Chain Fragment Variable: Recent Progress in Cancer Diagnosis and Therapy

Muñoz-López

Ribas‐Aparicio

Becerra-Báez

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…Full immunostaining protocol was performed as described, with minor modifications (24,25). Briefly, adrenal gland tissue sections (4 µm thick) were mounted on positively loaded glass slides and stained using the immunoperoxidase technique.…”

Section: Immunohistochemistry For Dhea/dheas and Ptenmentioning

confidence: 99%

“…The primary anti-DHEA antibody recognizes DHEA and DHEAS (24), hereby described as DHEA/DHEAS immune-positive cells, which were evaluated in the adrenal cortex of 14 post-mortem adrenal glands from individuals between the ages of 16-20 (n=8) and 41-43 years (n=6). Photomicrographs of the adrenal cortex are shown in Figure 3.…”

Section: Dhea/dheas Immunostaining and Cell Counts In Post-mortem Adrmentioning

confidence: 99%

From adrenarche to aging of adrenal zona reticularis: precocious female adrenopause onset

Nunes-Souza

Silveira

Mendes

et al. 2020

Endocrine Connections

Self Cite

View full text Add to dashboard Cite

Objective: Adaptive changes in dehydroepiandrosterone (DHEA) and sulfated-DHEA (DHEAS) production from adrenal zona reticularis (ZR) have been observed in normal and pathological conditions. Here we used three different cohorts to assess timing differences in DHEAS blood level changes and characterize the relationship between early blood DHEAS reduction and cell number changes in women ZR. Materials and methods: DHEAS plasma samples (n=463) were analyzed in 166 healthy prepubertal girls before pubarche (<9 years) and 324 serum samples from 268 adult females (31.9–83.8 years) without conditions affecting steroidogenesis. Guided by DHEAS blood levels reduction rate, we selected the age range for ZR cell counting using DHEA/DHEAS and phosphatase and tensin homolog (PTEN), tumor suppressor and cell stress marker, immunostaining, and hematoxylin stained nuclei of 14 post-mortem adrenal glands. Results: We confirmed that overweight girls exhibited higher and earlier DHEAS levels and no difference was found compared with the average European and South American girls with similar body-mass index (BMI). Adrenopause onset threshold (AOT) defined as DHEAS blood levels <2040 nmol/L was identified in >35% of the females >40 years old and associated with significantly reduced ZR cell number (based on PTEN and hematoxylin signals). ZR cell loss may in part account for lower DHEA/DHEAS expression, but most cells remain alive with lower DHEA/DHEAS biosynthesis. Conclusion: The timely relation between significant reduction of blood DHEAS levels and decreased ZR cell number at the beginning of the 40s suggests that adrenopause is an additional burden for a significant number of middle-aged women, and may become an emergent problem associated with further sex steroids reduction during the menopausal transition.

show abstract

“…Additionally, when tested in the presence of 0.75 µg·mL −1 and 10 µg·mL −1 of L. intermedia venom, Limab7 (50 pmol) was able to neutralize 100 and 80% of the hemolysis, respectively (data not shown). An irrelevant scFv anti-DHEA was also employed as a negative control [30].…”

Section: Intermedia Venom Neutralizationmentioning

confidence: 99%

Loxoscelism: Advances and Challenges in the Design of Antibody Fragments with Therapeutic Potential

Karim-Silva

Becker-Finco

Jiacomini

et al. 2020

Toxins

Self Cite

View full text Add to dashboard Cite

Envenoming due to Loxosceles spider bites still remains a neglected disease of particular medical concern in the Americas. To date, there is no consensus for the treatment of envenomed patients, yet horse polyclonal antivenoms are usually infused to patients with identified severe medical conditions. It is widely known that venom proteins in the 30-35 kDa range with sphingomyelinase D (SMasesD) activity, reproduce most of the toxic effects observed in loxoscelism. Hence, we believe that monoclonal antibody fragments targeting such toxins might pose an alternative safe and effective treatment. In the present study, starting from the monoclonal antibody LimAb7, previously shown to target SMasesD from the venom of L. intermedia and neutralize its dermonecrotic activity, we designed humanized antibody V-domains, then produced and purified as recombinant single-chain antibody fragments (scFvs). These molecules were characterized in terms of humanness, structural stability, antigen-binding activity, and venom-neutralizing potential. Throughout this process, we identified some blocking points that can impact the Abs antigen-binding activity and neutralizing capacity. In silico analysis of the antigen/antibody amino acid interactions also contributed to a better understanding of the antibody's neutralization mechanism and led to reformatting the humanized antibody fragment which, ultimately, recovered the functional characteristics for efficient in vitro venom neutralization. Key Contribution:The humanization of a mouse antibody V-domains able to neutralize Loxosceles intermedia venom paves the way for a new generation of anti-venom therapy. This study highlights the importance of understanding the antibody's mechanism of neutralization for appropriate design of innovative antidotes. Likewise, preserving favorable physico-chemical properties and antigen-binding activity is a challenge yet to be further addressed when considering pre-clinical trials.

show abstract

Biomolecular Engineering of Antidehydroepiandrosterone Antibodies: A New Perspective in Cancer Diagnosis and Treatment Using Single-Chain Antibody Variable Fragment

Cited by 7 publications

References 45 publications

Single-Chain Fragment Variable: Recent Progress in Cancer Diagnosis and Therapy

Single-Chain Fragment Variable: Recent Progress in Cancer Diagnosis and Therapy

From adrenarche to aging of adrenal zona reticularis: precocious female adrenopause onset

Loxoscelism: Advances and Challenges in the Design of Antibody Fragments with Therapeutic Potential

Contact Info

Product

Resources

About