Monoclonal antibody (MoAb) for cancer treatment has been greatly progressed during this decade. Six kinds of MoAbs are now in clinical use in Japan. Here we review on the development of MoAbs such as rituximab, bevacizumab and cetuximab. The characterization and the nomenclature of MoAb are also described. Panitumumab, a new MoAb targeting epithelial growth factor receptor(EGFR), and the resistance of colorectal cancer with KRAS mutation for anti-EGFR MoAbs are on recent topics. The concept of bevacizumab beyond progression (BBP) and the unfavorable results of bevacizumab in elder nonsmall cell lung carcinoma patients are so suggestive considering the strategy of the individualized cancer therapy. Finally, "drug lag" for the development of anti-cancer agents between Eastern and Western has to be discussed.

Antibody therapy in cancer

Purpose of review The purpose of this review is to describe the role of the human epidermal growth factor receptor 2 (HER2) as a biomarker and potential target in gynecologic malignancies and to describe contemporary updates in the use of anti-HER2 treatments for these cancers. Recent findings Approximately 25-30% of all patients with uterine serous carcinoma overexpress tumoral HER2. The anti-HER2 antibody trastuzumab represents an effective, targeted therapy with significant efficacy in the treatment of HER2-positive breast and gastric cancer. Recently, trastuzumab efficacy has also been demonstrated in a randomized controlled trial of women with advanced or recurrent uterine serous carcinoma. Additionally, trastuzumab may be effective in women with HER2-positive uterine carcinosarcoma. The role of anti-HER2 therapy is unclear in women with other gynecologic malignancies but is being evaluated. Summary HER2 amplification/overexpression is an effective therapeutic target in select gynecologic malignancies, and especially in the rare endometrial cancer subtype, uterine serous carcinoma. As anti-HER2-targeted therapies become increasingly available, more treatment options may become available for women with HER2-positive disease.

/pdf/targeting-human-epidermal-growth-factor-receptor-2-her2-in-1smkhs0raz.pdf

Targeting human epidermal growth factor receptor 2 (HER2) in gynecologic malignancies.

Trastuzumab (TZ) is a humanized monoclonal antibody targeted to the extracellular domain of human epidermal growth factor receptor 2 (HER2), a tyrosine kinase receptor. TZ is approved by the Food and Drug Administration (FDA) for the treatment of HER2-overexpressing early stage and metastatic breast cancer and HER2-overexpressing metastatic gastric cancer. For breast cancer, it is recommended as both a single agent and in combination with standard chemotherapy. In the last few years, TZ has also been used as a targeting ligand. Overexpression of HER2 in breast cancer and the presence of free surface functional groups on TZ provide an opportunity to use it as a targeting ligand. TZ can be conjugated to various nanoparticulate systems such as dendrimers, polymeric, and protein nanoparticles to target drug delivery. TZ-conjugated inorganic nanoparticles have been reported for imaging and diagnostic purposes. This review summarizes the applications of TZ both as a therapeutic agent and as a targeting ligand.

Biomedical applications of trastuzumab: as a therapeutic agent and a targeting ligand.

Cell motility and invasiveness are prerequisites for dissemination, and largely account for cancer mortality. We have identified an actionable kinase, spleen tyrosine kinase (SYK), which is keenly tightly associated with tumor progression in ovarian cancer. Here, we report that active recombinant SYK directly phosphorylates cortactin and cofilin, which are critically involved in assembly and dynamics of actin filament through phosphorylation signaling. Enhancing SYK activity by inducing expression of a constitutively active SYK mutant, SYK130E, increased growth factor-stimulated migration and invasion of ovarian cancer cells, which was abrogated by cortactin knockdown. Similarly, SYK inhibitors significantly decreased invasion of ovarian cancer cells across basement membrane in real-time transwell assays and in 3D tumor spheroid models. SYK inactivation by targeted gene knockout or by small molecule inhibition reduced actin polymerization. Collectively, this study reported a new mechanism by which SYK signaling regulates ovarian cancer cell motility and invasiveness, and suggest a target-based strategy to prevent or suppress the advancement of ovarian malignancies.

/pdf/inhibition-of-ovarian-tumor-cell-invasiveness-by-targeting-1a9vsiikju.pdf

Inhibition of ovarian tumor cell invasiveness by targeting SYK in the tyrosine kinase signaling pathway

Most high-throughput screening (HTS) systems studying the cytotoxic effect of chimeric antigen receptor (CAR) T cells on tumor cells rely on two-dimensional cell culture that does not recapitulate the tumor microenvironment (TME). Tumor spheroids, however, can recapitulate the TME and have been used for cytotoxicity assays of CAR T cells. But a major obstacle to the use of tumor spheroids for cytotoxicity assays is the difficulty in separating unbound CAR T and dead tumor cells from spheroids. Here, we present a three-dimensional hanging spheroid plate (3DHSP), which facilitates the formation of spheroids and the separation of unbound and dead cells from spheroids during cytotoxicity assays.The 3DHSP is a 24-well plate, with each well composed of a hanging dripper, spheroid wells, and waste wells. In the dripper, a tumor spheroid was formed and mixed with CAR T cells. In the 3DHSP, droplets containing the spheroids were deposited into the spheroid separation well, where unbound and dead T and tumor cells were separated from the spheroid through a gap into the waste well by tilting the 3DHSP by more than 20°. Human epidermal growth factor receptor 2 (HER2)-positive tumor cells (BT474 and SKOV3) formed spheroids of approximately 300-350 μm in diameter after 2 days in the 3DHSP. The cytotoxic effects of T cells engineered to express CAR recognizing HER2 (HER2-CAR T cells) on these spheroids were directly measured by optical imaging, without the use of live/dead fluorescent staining of the cells. Our results suggest that the 3DHSP could be incorporated into a HTS system to screen for CARs that enable T cells to kill spheroids formed from a specific tumor type with high efficacy or for spheroids consisting of tumor types that can be killed efficiently by T cells bearing a specific CAR.The results suggest that the 3DHSP could be incorporated into a HTS system for the cytotoxic effects of CAR T cells on tumor spheroids. 

/pdf/3d-hanging-spheroid-plate-for-high-throughput-car-t-cell-1u6iv1j0.pdf

3D hanging spheroid plate for high-throughput CAR T cell cytotoxicity assay

Objective Ovarian cancer is 1 kind of a highly malignant gynecologic tumor, and current treatments have not achieved satisfactory effects. Human epidermal growth factor receptor 2 (HER2)–targeted therapies including trastuzumab and trastuzumab-DM1 (T-DM1) (antibody-cytotoxic drug conjugates) have been applied to treat HER2-overexpressing breast cancers in clinic. In the present study, we explored whether T-DM1 could effectively treat HER2-positive human ovarian carcinoma in vitro and in vivo. Methods HER2 expressions of 6 ovarian cancer cell lines and 2 breast carcinoma cell lines were validated, and the binding capacity of T-DM1 to HER2-positive ovarian cancer SKOV3 cells were analyzed by flow cytometry. Nude mice bearing intraperitoneal and subcutaneous SKOV3 xenografts were used to investigate the antitumor effect of T-DM1. Results High HER2 expressions in SKOV3 cell lines were detected. The binding capacity of T-DM1 to HER2-positive SKOV3 cells was in a similar manner comparing with trastuzumab. In vitro, T-DM1 showed strong growth inhibitory on SKOV3 cells, with IC50 values of 0.15 nmol/L. Nude mice bearing intraperitoneal and subcutaneous SKOV3 xenografts were used to investigate the antitumor effects of T-DM1 in vivo. In subcutaneous xenografts model, T-DM1 (30 mg/kg and 10 mg/kg) indicated significant anticancer effects. It is noteworthy that tumors were completely eradicated in the T-DM1 (30 mg/kg) group, and no regrowth was observed in a long time after the termination of the treatment. In the peritoneal xenograft model, tumor nodules in 3 of 7 mice were hardly observed in the abdominal cavity of mice after intraperitoneal injection of T-DM1 (30 mg/kg). At the same time, tumor nodules from the other 4 mice weighed on the average of only 0.07 g versus 1.77 g in control group. Conclusions Our data showed that T-DM1 possessed promising antitumor effects on HER2-overexpressing ovarian cancer in mouse model, which provided valuable references for the future clinical trials.

Eradication of Growth of HER2-Positive Ovarian Cancer With Trastuzumab-DM1, an Antibody-Cytotoxic Drug Conjugate in Mouse Xenograft Model

Efficient expression, purification and characterization of native human cystatin C in Escherichia coli periplasm.

Methods Cells were cultivated properly to obtain 3E10 CREPT monoclonal antibody cells in the logarithmic growth stage. Monoclonal antibody cells were injected into the abdominal cavity of sensitized mice. The flowing ascites were observed for 7-15 days. The antibody protein was obtained by collection, filtration, dilution, loading, and chromatography. Furthermore, its binding force was detected by SDS-PAGE and Western blot techniques. Results The antibody protein was successfully obtained with a purity of 1895 μg/mL with high liveness. Conclusion This study establishes a one-step purification method for obtaining monoclonal antibody with high liveness and purity for CREPT ascites antibody. This method is simple to perform and lays a foundation for the preparation and purification of humanized monoclonal antibodies in the future. In addition, it provides a basis for further research to investigate how CREPT affects the occurrence and development of different tumors.

/pdf/purification-and-analysis-of-the-crept-antibody-from-mouse-2evlfi17.pdf

Purification and Analysis of the CREPT Antibody from Mouse Ascites

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Jun Li

Author Tools

Chat about Author

Papers

Eradication of Growth of HER2-Positive Ovarian Cancer With Trastuzumab-DM1, an Antibody-Cytotoxic Drug Conjugate in Mouse Xenograft Model

Efficient expression, purification and characterization of native human cystatin C in Escherichia coli periplasm.

Purification and Analysis of the CREPT Antibody from Mouse Ascites