• Title/Summary/Keyword: Immunogenicity

Search Result 241, Processing Time 0.024 seconds

Development of Protein Drugs by PEGylation Technology (PEGylation 기술을 이용한 단백질 의약품 개발)

  • Na, Dong-Hee
    • KSBB Journal
    • /
    • v.26 no.4
    • /
    • pp.293-299
    • /
    • 2011
  • PEGylation, the attachment of polyethylene glycol (PEG) to proteins, is currently main technology for improving efficacy of protein drugs. This technology can prolong the plasma half-life, augment the in vivo stability, and diminish the immunogenicity of therapeutic proteins. Therefore, PEGylated proteins have the enhanced therapeutic efficacy and the reduced undesirable effects versus their native therapeutics. Since the first PEGylated protein product appeared on the market in the early 1990s, currently ten PEGylated protein products have been launched. These marketed drug products have proved the applicability and safety of the PEGylation technology. This review presents overview of PEGylation technology and addresses characteristics of PEGylation methods applied for the development of several protein drugs.

Chemical Modification of Sheep Hemoglobin with Methoxy-Polyethylene Glycol

  • Jeong, Seong-Tae;Byun, Si-Myung
    • BMB Reports
    • /
    • v.29 no.3
    • /
    • pp.261-265
    • /
    • 1996
  • Sheep hemoglobin (SHb) was modified with methoxy-polyethylene glycol (mPEG) to develop a potential blood substitute. mPEG has been used to decrease antigenicity and immunogenicity of foreign proteins. When the mPEG was attached to SHb, the modified hemoglobins showed decreased electrophoretic mobility on SDS-PAGE and decreased free amino groups. When the remaining free amino groups of mPEG modified SHb were determined by TNBS free amino group titration methods. about 34% of total free amino groups were modified with mPEG. This mPEG-SHb conjugate of 34% amino groups modified showed no precipitation by double immunodiffusion with polyclonal antibodies against SHb. This modified hemoglobin still has oxygen transport activity. So this antigenicity decreased hemoglobin may be used in humans as a potential blood substitute.

  • PDF

Therapeutic aptamers: developmental potential as anticancer drugs

  • Lee, Ji Won;Kim, Hyun Jung;Heo, Kyun
    • BMB Reports
    • /
    • v.48 no.4
    • /
    • pp.234-237
    • /
    • 2015
  • Aptamers, composed of single-stranded DNA or RNA oligonucleotides that interact with target molecules through a specific three-dimensional structure, are selected from pools of combinatorial oligonucleotide libraries. With their high specificity and affinity for target proteins, ease of synthesis and modification, and low immunogenicity and toxicity, aptamers are considered to be attractive molecules for development as anticancer therapeutics. Two aptamers - one targeting nucleolin and a second targeting CXCL12 - are currently undergoing clinical trials for treating cancer patients, and many more are under study. In this mini-review, we present the current clinical status of aptamers and aptamer-based cancer therapeutics. We also discuss advantages, limitations, and prospects for aptamers as cancer therapeutics. [BMB Reports 2015; 48(4): 234-237]

Production of the recombinant fibronectin-binding protein of Staphylococcus aureus (Staphylococcus aureus의 재조합 fibronectin-binding protein의 생산)

  • kim, Doo;Cheong, Cha-ryong;Park, Hee-myong;Han, Hong-ryul
    • Korean Journal of Veterinary Research
    • /
    • v.37 no.4
    • /
    • pp.875-882
    • /
    • 1997
  • To produce the recombinant fibronectin-binding protein(FnBP) for development of subunit vaccine against Staphylococcus aureus. The fnbp gene was amplified from the chromosomal DNA of S aureus KNU 196 strain using the polymerase chain reaction, and cloned into pGEX-4T-2. Then, the recombinant FnBP fused with glutathione-S-transferase was produced in E coli, purified by affinity chromatography, and identified its antigenicity and immunogenicity by Western blot. The recombinant FnBP produced in this study is considered to have the same property of native FnBP purified from S aureus, and is expected to be useful as a candidate for S aureus subunit vaccine.

  • PDF

Antibodies against Nitric Oxide Damaged Poly L-Tyrosine and 3-Nitrotyrosine Levels in Systemic Lupus Erythematosus

  • Khan, Fozia;Ali, Rashid
    • BMB Reports
    • /
    • v.39 no.2
    • /
    • pp.189-196
    • /
    • 2006
  • Alterations in the amino acid structure or sequence can generate neo-epitopes from self-proteins causing autoaggressive immune attack. Reactive nitrogen species are an important factor that induces post-translational modification of proteins by cellular reduction and oxidation mechanism; cysteinyl-nitrosylation or tyrosine nitration leading to potentially pathogenic pathways. It was thought of interest to investigate the immunogenicity of nitrated poly L-tyrosine vis-$\`{a}$-vis its possible role in the induction of antibodies in systemic lupus erythematosus (SLE). Commercially available poly L-tyrosine was exposed to nitrating species and the damage was monitored by UV spectroscopy and alkaline gel electrophoresis. The results indicated the formation of 3-nitrotyrosine. Nitrated poly L-tyrosine induced higher titre antibodies as compared to the native form. Nitrated poly L-tyrosine was recognized by the autoantibodies present in the sera of patients suffering from SLE by enzyme immunoassays and band shift assay. The possible role of nitrated self-proteins has been discussed in the production of circulating anti-DNA antibodies in SLE.

Study of Cell-mediated Response in Mice by HPV16 L1 Virus-like Particles Expressed in Saccharomyces cerevisiae

  • Woo, Mi-Kyung;Hur, Sook-Jin;Park, Sue-NIe;Kim, Hong-Jin
    • Journal of Microbiology and Biotechnology
    • /
    • v.17 no.10
    • /
    • pp.1738-1741
    • /
    • 2007
  • The first vaccine against human papillomaviruses (HPV) formulated with HPV16 L1 virus-like particles (VLPs) produced in yeast was approved by the FDA in June 2006. Nevertheless, there have been few studies of the immunogenicity in mice of VLPs. In this study, we evaluated the cell-mediated immune response to VLPs produced in Saccharomyces cerevisiae. After immunization of mice with HPV16 L1 VLPs, we measured splenocytes proliferation and the levels of IFN$_{\gamma}$, IL2, IL4, and IL5. Splenocytes proliferation was significantly increased and a mixed Th1/Th2 response was indicated. IgG subtype immunoresponses were strongly induced and IgG1 titers were higher than those of IgG2a.

Statistical Considerations in the Design of Biosimilar Cancer Clinical Trials

  • Ahn, Chul;Lee, Seung-Chun
    • The Korean Journal of Applied Statistics
    • /
    • v.24 no.3
    • /
    • pp.495-503
    • /
    • 2011
  • When a patent of an innovative (brand-name) small-molecule drug expires, generic copies of the innovative drug may be marketed if their therapeutic equivalence to the innovative drug has been shown. The small-molecule drugs are considered therapeutically equivalent and can be used interchangeably if two drugs are shown to be pharmaceutically equivalent with identical active substance and bioequivalent with comparable pharmacokinetics in a crossover clinical trial. However, the therapeutic equivalence paradigm cannot be applied to biosimilars since the active ingredients of biosimilars are huge molecules with complex and heterogeneous structures, and these molecules are difficult to replicate in every detail. The European Medicine Agency(EMEA) has introduced a regulatory biosimilar pathway which mandates clinical trials to show therapeutic equivalence. In this paper, we discuss statistical considerations in the design and analysis of biosimilar cancer clinical trials.

Production of Recombinant Anti-Cancer Vaccines in Plants

  • Lee, Jeong Hwan;Ko, Kisung
    • Biomolecules & Therapeutics
    • /
    • v.25 no.4
    • /
    • pp.345-353
    • /
    • 2017
  • Plant expression systems have been developed to produce anti-cancer vaccines. Plants have several advantages as bioreactors for the production of subunit vaccines: they are considered safe, and may be used to produce recombinant proteins at low production cost. However, several technical issues hinder large-scale production of anti-cancer vaccines in plants. The present review covers design strategies to enhance the immunogenicity and therapeutic potency of anti-cancer vaccines, methods to increase vaccine-expressing plant biomass, and challenges facing the production of anti-cancer vaccines in plants. Specifically, the issues such as low expression levels and plant-specific glycosylation are described, along with their potential solutions.

Nucleic Acid Aptamers: New Methods for Selection, Stabilization, and Application in Biomedical Science

  • Kong, Hoon Young;Byun, Jonghoe
    • Biomolecules & Therapeutics
    • /
    • v.21 no.6
    • /
    • pp.423-434
    • /
    • 2013
  • The adoption of oligonucleotide aptamer is well on the rise, serving an ever increasing demand for versatility in biomedical field. Through the SELEX (Systematic Evolution of Ligands by EXponential enrichment), aptamer that can bind to specific target with high affinity and specificity can be obtained. Aptamers are single-stranded nucleic acid molecules that can fold into complex three-dimensional structures, forming binding pockets and clefts for the specific recognition and tight binding of any given molecular target. Recently, aptamers have attracted much attention because they not only have all of the advantages of antibodies, but also have unique merits such as thermal stability, ease of synthesis, reversibility, and little immunogenicity. The advent of novel technologies is revolutionizing aptamer applications. Aptamers can be easily modified by various chemical reactions to introduce functional groups and/or nucleotide extensions. They can also be conjugated to therapeutic molecules such as drugs, drug containing carriers, toxins, or photosensitizers. Here, we discuss new SELEX strategies and stabilization methods as well as applications in drug delivery and molecular imaging.