Identification of cytomegalovirus (CMV)pp65 antigen-specific human monoclonal antibodies using single B cell-based antibody gene cloning from melanoma patients

Iizuka, Akira; Komiyama, Masaru; Tai, Sachiko; Oshita, Chie; Kurusu, Ayumi; Kume, Akiko; Ozawa, Kenji; Nakamura, Yoji; Ashizawa, Tadashi; Yamamoto, Akifumi; Yamazaki, Naoya; Yoshikawa, Shusuke; Kiyohara, Yoshio; Yamaguchi, Ken; Akiyama, Yasuto

doi:10.1016/j.imlet.2010.09.013

Cited by 8 publications

(3 citation statements)

References 27 publications

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“…Rapid isolation of dengue-neutralizing antibodies from human antigen-specific memory B-cell cultures [224] and characterization of antigen-specific B cells in the peripheral blood of DENV-immune individuals [213] were both reported. In another example, Iizuka and colleagues described the identification of cytomegalovirus pp65 antigen-specific human mAbs using single B cell-based antibody gene cloning [225]. For rotavirus, the single B cell method was performed to analyze the rotavirus antibody gene repertoire of VP6-specific B cells in naive and memory B cell subsets [226] and generate rotavirus-specific human mAbs by sorting single B cells from small-intestinal mucosa [227].…”

Section: Methodologies For Developing Therapeutic Antibodiesmentioning

confidence: 99%

Development of therapeutic antibodies for the treatment of diseases

et al. 2020

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It has been more than three decades since the first monoclonal antibody was approved by the United States Food and Drug Administration (US FDA) in 1986, and during this time, antibody engineering has dramatically evolved. Current antibody drugs have increasingly fewer adverse effects due to their high specificity. As a result, therapeutic antibodies have become the predominant class of new drugs developed in recent years. Over the past five years, antibodies have become the best-selling drugs in the pharmaceutical market, and in 2018, eight of the top ten bestselling drugs worldwide were biologics. The global therapeutic monoclonal antibody market was valued at approximately US$115.2 billion in 2018 and is expected to generate revenue of $150 billion by the end of 2019 and $300 billion by 2025. Thus, the market for therapeutic antibody drugs has experienced explosive growth as new drugs have been approved for treating various human diseases, including many cancers, autoimmune, metabolic and infectious diseases. As of December 2019, 79 therapeutic mAbs have been approved by the US FDA, but there is still significant growth potential. This review summarizes the latest market trends and outlines the preeminent antibody engineering technologies used in the development of therapeutic antibody drugs, such as humanization of monoclonal antibodies, phage display, the human antibody mouse, single B cell antibody technology, and affinity maturation. Finally, future applications and perspectives are also discussed.

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Section: Methodologies For Developing Therapeutic Antibodiesmentioning

confidence: 99%

Development of therapeutic antibodies for the treatment of diseases

et al. 2020

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“…The purified trastuzumab scFv fragment antibody was analyzed for binding capacity using SPR and flow cytometry. Anti-cytomegalovirus (CMV)pp65 human scFv antibody that was produced in E. coli in our laboratory (15) was used as a negative control in the flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

The identification of affinity peptide ligands specific to the variable region ofhuman antibodies

et al. 2014

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Of all potential biological therapeutics, monoclonal antibody (mAb)-based therapies are becoming the dominant focus of clinical research. In particular, smaller recombinant antibody fragments such as single-chain variable fragments (scFv) have become the subject of intense focus. However, an efficient affinity ligand for antibody fragment purification has not been developed. In the present study, we designed a consensus sequence for the human antibody heavy or light chain-variable regions (Fv) based on the antibody sequences available in the ImMunoGeneTics information system (IMGT), and synthesized these consensus sequences as template Fv antibodies. We then screened peptide ligands that specifically bind to the repertoire-derived human Fv consensus antibody using a 12-mer-peptide library expressed-phage display method. Subsequently, 1 peptide for the VH template and 8 peptides for the VK template were selected as the candidate ligands after 4 rounds of panning the phage display. Using peptide-bead-based immunoprecipitation, the code-4 and code-13 peptides showed recovery rates of the VH and VK templates that were 20-30% and 40-50%, respectively. Both peptides exhibited better recovery rates for trastuzumab scFv (approximately 40%). If it were possible to identify the best combination of VH and VK-binding peptides among the ligand peptides suitable for the human mAb Fv sequence, the result could be a promising purification tool that might greatly improve the cost efficiencies of the purification process.In recent years, advances in protein research have resulted in several monoclonal antibody (mAb) therapies for cancer, infections and immunological disorders, which have increasingly become the preferred choice out of the many available biological therapeutics. In the United States which is the largest market for mAb therapeutics worldwide, more than 20 mAbs have been approved for clinical use and over 200 mAb candidates are in the clinical pipeline (21,25). Monoclonal antibody therapeutics are playing an important role in the clinical field and recombinant antibodies are predicted to account for more than 30% of all revenues in the biopharmaceutical market (1,4,22

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“…The ELISA for detecting human antibodies and the control reaction system were described previously (18). MAGE antigen proteins with a glutathione S-transferase (GST) tag were all purchased from Abnova Corp., Taipei, Taiwan.…”

Section: Methodsmentioning

confidence: 99%

Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial

et al. 2012

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Metastatic and chemoresistant melanoma can be a good target of immunotherapy because it is an intractable cancer with a very poor prognosis. Previously, we tested a dendritic cell (DC)-based phase I vaccine, and confirmed that it was safe. In the present study, we performed a phase II trial of a DC vaccine for metastatic melanoma patients with mainly the HLA-A24 genotype, and investigated the efficacy of the vaccine. Twenty-four patients with metastatic melanoma were enrolled into a phase II study of DC-based immunotherapy. The group included 19 HLA-A24-positive (A*2402) patients and 3 HLA-A2-positive (A*0201) patients. The protocol for DC production was similar to that in the phase I trial. Briefly, a cocktail of 5 melanoma-associated synthetic peptides (gp100, tyrosinase, MAGE-A2, MAGE-A3 and MART-1 or MAGE-A1) restricted to HLA-A2 or A24 and KLH were used for DC pulsing. Finally, DCs were injected subcutaneously (s.c.) into the inguinal region in the dose range of 1–5×107 per shot. The DC ratio (lin-HLA-DR+) of the vaccine was 38.1±13.3% and the frequency of CD83+ DCs was 25.7±20.8%. Other parameters regarding DC processing were not different from phase I. Immune response-related parameters including the ELISPOT assay, DTH reaction to peptide or KLH, DC injection numbers were shown to be related to a good prognosis. The ELISPOT reaction was positive in 75% of the patients vaccinated. The increase of anti-melanoma antigen antibody titer before vaccination was also shown to be a prognosis factor, but that post-vaccination was not. Based on immunohistochemical analysis, CD8 and IL-17 were not involved in the prognosis. Adverse effects of more than grade III were not seen. Overall survival analysis revealed a significant survival prolongation effect in DC-given melanoma patients. These results suggest that peptide cocktail-treated DC vaccines may be a safe and effective therapy against metastatic melanoma in terms of prolongation of overall survival time.

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Identification of cytomegalovirus (CMV)pp65 antigen-specific human monoclonal antibodies using single B cell-based antibody gene cloning from melanoma patients

Cited by 8 publications

References 27 publications

Development of therapeutic antibodies for the treatment of diseases

Development of therapeutic antibodies for the treatment of diseases

The identification of affinity peptide ligands specific to the variable region ofhuman antibodies

Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial

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