• Title/Summary/Keyword: Biologics

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Development of Bispecific Antibody for Cancer Immunotherapy: Focus on T Cell Engaging Antibody

  • Dain Moon;Nara Tae;Yunji Park;Seung-Woo Lee;Dae Hee Kim
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.4.1-4.22
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    • 2022
  • In the era of immunotherapeutic control of cancers, many advances in biotechnology, especially in Ab engineering, have provided multiple new candidates as therapeutic immuno-oncology modalities. Bispecific Abs (BsAbs) that recognize 2 different antigens in one molecule are promising drug candidates and have inspired an upsurge in research in both academia and the pharmaceutical industry. Among several BsAbs, T cell engaging BsAb (TCEB), a new class of therapeutic agents designed to simultaneously bind to T cells and tumor cells via tumor cell specific antigens in immunotherapy, is the most promising BsAb. Herein, we are providing an overview of the current status of the development of TCEBs. The diverse formats and characteristics of TCEBs, in addition to the functional mechanisms of BsAbs are discussed. Several aspects of a new TCEB-Blinatumomab-are reviewed, including the current clinical data, challenges of patient treatment, drawbacks regarding toxicities, and resistance of TCEB therapy. Development of the next generation of TCEBs is also discussed in addition to the comparison of TCEB with current chimeric antigen receptor-T therapy.

Immunopathology and Immunotherapy of Inflammatory Skin Diseases

  • Ahreum Song;Sang Eun Lee;Jong Hoon Kim
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.7.1-7.20
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    • 2022
  • Recently, there have been impressive advancements in understanding of the immune mechanisms underlying cutaneous inflammatory diseases. To understand these diseases on a deeper level and clarify the therapeutic targets more precisely, numerous studies including in vitro experiments, animal models, and clinical trials have been conducted. This has resulted in a paradigm shift from non-specific suppression of the immune system to selective, targeted immunotherapies. These approaches target the molecular pathways and cytokines responsible for generating inflammatory conditions and reinforcing feedback mechanisms to aggravate inflammation. Among the numerous types of skin inflammation, psoriasis and atopic dermatitis (AD) are common chronic cutaneous inflammatory diseases. Psoriasis is a IL-17-mediated disease driven by IL-23, while AD is predominantly mediated by Th2 immunity. Autoimmune bullous diseases are autoantibody-mediated blistering disorders, including pemphigus and bullous pemphigoid. Alopecia areata is an organ-specific autoimmune disease mediated by CD8+ T-cells that targets hair follicles. This review will give an updated, comprehensive summary of the pathophysiology and immune mechanisms of inflammatory skin diseases. Moreover, the therapeutic potential of current and upcoming immunotherapies will be discussed.

Evaluation for foot-and-mouth disease vaccines in South Korea by the test for national lot release (구제역 백신의 국가출하승인검정을 통한 품질 평가)

  • Kim, Mun-Hyeon;Seo, Min-Goo;Lee, Hyang-Sim;Kim, Ji-Yeon;Kim, Ji-Ye;Kim, Yong-Sang;Kim, Yeon-Hee
    • Korean Journal of Veterinary Service
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    • v.42 no.4
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    • pp.285-288
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    • 2019
  • Foot-and-mouth disease (FMD) causes economic problems in livestock industry because of fast spread and inducing low productivity. FMD outbreaks occurred in South Korea over the period from 2000 to 2019. Vaccination is the most practical and effective means of controlling or preventing these outbreaks, and a national vaccination policy has been in place for all FMD-susceptible animals since 2010. To prevent and control of FMD, South Korea has been using vaccines imported from the United Kingdom, Argentina, and Russia. The Animal and Plant Quarantine Agency of South Korea oversees continuous quality control of imported FMD vaccines. FMD vaccines were evaluated characteristics, sterility, pH, inactivation, safety, potency test by Korean FMD vaccine standard assay (Test for National Lot Release). The 6 company vaccines (A~F) were used Test for National Lot Release by each method. We evaluated quality of each FMD vaccine from 2015 to 2019. All batch of vaccine showed good quality control and were passed the Test for National Lot Release. The serotypes of vaccine are increasingly changing to multiple vaccine because the FMD was outbreak by various serotype virus in South Korea. Furthermore, this data may be useful as a basis for ensuring the quality of FMD vaccines and for base data to manage them. Additional study is required to simple approach for rapid evaluation of quality and antigen content identification in vaccines.

Development of an attenuated vaccine strain from a korean respiratory type infectious bronchitis virus (한국호흡기형 닭전염성기관지염 생독백신주의 작성)

  • Choi, Kang-Seuk;Jeon, Woo-Jin;Lee, Eun-Kyoung;Kye, Soo-Jeong;Park, Mi-Ja;Kwon, Jun-Hun
    • Korean Journal of Veterinary Research
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    • v.51 no.3
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    • pp.193-201
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    • 2011
  • An attenuated vaccine strain AVR1/08 of Korean respiratory type of infectious bronchitis virus (IBV) was developed by 89th passages of IBV D85/06 strain in chicken eggs. The AVR1/08 strain had higher virus titer at least 20 times ($10^{1.3}$) than the parent virus D85/06 by egg inoculation method. The AVR1/08 strain had a single point mutation (S to Y) at position 56 of spike protein of IBV compared to parent virus IBV D85/06 strain. The mutation was observed consistently at viruses after 47th passage in chicken eggs. The AVR1/08 strain showed no virulence even after 6 passages in chickens and all chickens inoculated induced anti-IBV antibody 14 days after vaccination. The AVR1/08 strain had broad protective efficacy against QX type Korean nephropathogenic virus (Q43/06 strain), KM91 type Korean nephropathogenic virus (KM91 strain) and Korean respiratory virus (D85/06 strain). In contrast, Massachusetts (Mass) type attenuated vaccine strain H120 showed protection of 37.5 to 50% against these three viruses. Our results indicate that the AVR1/08 strain has potential as an attenuated vaccine effective in controlling IBVs circulating in Korea.

Analysis and Estimation for Market Share of Biologics based on Google Trends Big Data (구글 트렌드 빅데이터를 통한 바이오의약품의 시장 점유율 분석과 추정)

  • Bong, Ki Tae;Lee, Heesang
    • Journal of Korean Society of Industrial and Systems Engineering
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    • v.43 no.2
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    • pp.14-24
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    • 2020
  • Google Trends is a useful tool not only for setting search periods, but also for providing search volume to specific countries, regions, and cities. Extant research showed that the big data from Google Trends could be used for an on-line market analysis of opinion sensitive products instead of an on-site survey. This study investigated the market share of tumor necrosis factor-alpha (TNF-α) inhibitor, which is in a great demand pharmaceutical product, based on big data analysis provided by Google Trends. In this case study, the consumer interest data from Google Trends were compared to the actual product sales of Top 3 TNF-α inhibitors (Enbrel, Remicade, and Humira). A correlation analysis and relative gap were analyzed by statistical analysis between sales-based market share and interest-based market share. Besides, in the country-specific analysis, three major countries (USA, Germany, and France) were selected for market share analysis for Top 3 TNF-α inhibitors. As a result, significant correlation and similarity were identified by data analysis. In the case of Remicade's biosimilars, the consumer interest in two biosimilar products (Inflectra and Renflexis) increased after the FDA approval. The analytical data showed that Google Trends is a powerful tool for market share estimation for biosimilars. This study is the first investigation in market share analysis for pharmaceutical products using Google Trends big data, and it shows that global and regional market share analysis and estimation are applicable for the interest-sensitive products.

Anti-complement Effects of Anion-Substituted Poly(vinyl alcohol) Membranes

  • Ryu, Kyu-Eun;Rhim, Hyang-Shuk;Park, Chong-Won;Chun, Heung-Jae;Hong, Seung-Hwa;Kim, Young-Chai;Lee, Young-Moo
    • Macromolecular Research
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    • v.12 no.1
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    • pp.46-52
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    • 2004
  • In a continuation of our previous studies on blood compatibility profiles of anion-substituted poly(vinyl alcohol) (PVA) membranes, in which hydroxyl groups have been replaced with carboxymethyl (C-PVA) and sulfonyl groups (S-PVA), we have studied the activation of complement components and the changes in white cell and platelet count in vitro and compared them with those of unmodified PVA, Cuprophane, and low-density polyethylene. Complement activation of fluid phase components, C3a, Bb, iC3b, and SC5b-9, and of bound phases, C3c, C3d, and SC5b-9, were assessed by enzyme-linked immunosorbent assay (ELISA) and immunoblot, respectively. The changes in the number of white cells and platelets following complement activation were counted using a Coulter counter. C-PVA and S-PVA activated C3 to a lesser extent than did PVA, which we attribute to the diminished level of surface nucleophiles of the samples. In addition, C- and S-PVA exhibit increased inhibition of Bb production, resulting in a decrease in the extent of C5 activation. Consequently, because of the reduced activation of C3 and C5, C- and S-PVA samples cause marked decreases in the SC5b-9 levels in plasma. We also found that the negatively charged sulfonate and carboxylate groups of the samples cause a greater extent of adsorbtion of the positively charged anaphylatoxins, C3a and C5a, because of strong electrostatic attraction, which in turn provides an inhibition of chemotaxis and activation of leukocytes. The ability to inhibit complement production, together with the binding ability of anaphylatoxins of the C- and S-PVA samples, leads to a prominent decrease in lysis of leukocytes as well as activation of platelets.

Artificial Dermis Composed of Gelatin, Hyaluronic Acid and (1\longrightarrow3),(1\longrightarrow6)-$\beta$-Glucan

  • Lee, Sang-Bong;Jeon, Hyun-Wook;Lee, Young-Woo;Cho, Seong-Kwan;Lee, Young-Woo;Song, Kang-Won;Park, Moon-Hyang;Hong, Sung-Hwa
    • Macromolecular Research
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    • v.11 no.5
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    • pp.368-374
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    • 2003
  • Porous scaffolds composed of gelatin and polysaccharides such as hyaluronic acid and $\beta$-glucan were prepared by using the freeze-drying method after cross-linking with l-ethyl-(3-3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). The scaffold had an inter-connected pore structure with the sufficient pore size for use as a support for the growth of fibroblasts. Results for the contact angle and cell attachment confirmed that high gelatin content in a mixture was suitable for cellular attachment and distribution in two- or three-dimensional fibroblast cultures. However, the addition of polysaccharides aroused the synergistic effects of morphologic and mechanical property of gelatin-based scaffolds. To prepare the artificial dermis for the wound dressing to mimic the normal human dermal skin, fibroblasts were isolated from a child's foreskin, and cultured in gelatin-based scaffolds. An in vivo study showed that the artificial dermis containing the fibroblasts enhanced the wound healing rate and re-epithelialization of a full-thickness skin defect rather than the acellular scaffold after one week.

Development of Alternative Testing Methods without Hazardous Reagents used in Korean Pharmaceutical Codex (고시의약품 시험에 사용되는 유해시약 대체 시험법 개발)

  • Kim, Hee-Yun;Kang, Hyun-Kyung;Choi, Seon-Hee;Bang, Su-Jin;Han, Kyung-Jin;Choi, Sung-Hee;Kim, Jin-Hee;Lee, Hwa-Jung;Kang, Chan-Soon
    • YAKHAK HOEJI
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    • v.54 no.2
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    • pp.142-149
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    • 2010
  • Development of alternative testing methods for the replacement of hazardous reagents with less hazardous ones is strongly enforced because exposure of human and environment to hazardous reagents are restricted and hazardous reagents are gradually prohibited from using in various testing methods. Thus, in this study, we developed 8 monographs from the Korean Pharmaceutical Codex by substituting the use of the hazardous reagents including ICH class 1 such as benzene, chloroform and dioxane to the use of less toxic ones like ICH class 2 or 3 reagents. We also improved their qualification and quantification performance. Among 8 monographs, the 6 newly developed TLC methods for the identification of nifedipine, oxolamine citrate, ketoprofen lysinate, chlorquinaldol, retinol acetate, and riboflavin showed a clear spot of corresponding material without any interference in spite of the replacement with ICH class 2 or 3 reagents. For the quantification of domperidone and trimebutine, HPLC methods were developed for the substitution of UV/VIS spectrometry and titrimetry, respectively. These HPLC methods were validated for the linearity, recovery, reproducibility, and inter-laboratory variations. In conclusion, the newly developed methods could be expected to become valuable tools for revising the Korean Pharmaceutical Codex.

Fabrication of Ultra Fine β-phase Ti-Nb-Sn-HA Composite by Pulse Current Activated Sintering

  • Woo, Kee-Do;Wang, Xiaopeng;Kang, Duck-Soo;Kim, Sang-Hyuk;Woo, Jeong-Nam;Park, Sang-Hoon;Liuc, Zhiguang
    • Journal of Powder Materials
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    • v.17 no.6
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    • pp.443-448
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    • 2010
  • The $\beta$ phase Ti-Nb-Sn-HA bio materials were successfully fabricated by high energy mechanical milling and pulse current activated sintering (PCAS). Ti-6Al-4V ELI alloy has been widely used as biomaterial. But the Al has been inducing Alzheimer disease and V is classified as toxic element. In this study, ultra fine sized Ti-Nb-Sn-HA powder was produced by high energy mechanical milling machine. The $\beta$ phase Ti-Nb-Sn-HA powders were obtained after 12hr milling from $\alpha$ phase. And ultra fine grain sized Ti-Nb-Sn-HA composites could be fabricated using PCAS without grain growth. After sintering, the microstructures and phase-transformation of Ti-Nb-Sn-HA biomaterials were analyzed by scanning electron microscope (SEM) and X-ray diffraction (XRD). The relative density was obtained by Archimedes principle and the hardness was measured by Vickers hardness tester. The $\beta$-Ti phase was obtained after 12h milling. As result of hardness and relative density, 12h milled Ti-Nb-Sn-HA composite has the highest values.

Economic Factors as Major Determinants of Ustekinumab Drug Survival of Patients with Chronic Plaque Psoriasis in Korea

  • Choi, Chong Won;Yang, Seungkeol;Jo, Gwanghyun;Kim, Bo Ri;Youn, Sang Woong
    • Annals of dermatology
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    • v.30 no.6
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    • pp.668-675
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    • 2018
  • Background: Drug survival, defined as the time until discontinuation, is a parameter reflecting real-world therapeutic effectiveness. Few studies have examined the influence of economic factors on the drug survival of biologic agents for psoriasis, particularly in Asian countries. Objective: To determine the drug survival for ustekinumab in real-life settings and investigate the factors affecting drug survival for psoriasis patients in Korea. Methods: We evaluated 98 psoriasis patients who were treated with ustekinumab at a single center. We analyzed the efficacy and drug survival of ustekinumab. Cox proportional hazard analysis and competing risk regression analysis were performed to reveal the factors affecting the drug survival of ustekinumab. Results: The overall mean drug survival was 1,596 days (95% confidence interval [CI], 904~2,288). Among the 39 cessations of ustekinumab treatment, 9 (23.1%) patients discontinued treatment after experiencing satisfactory results. Multivariate Cox proportional hazard analysis revealed that paying on patients' own expense was the major predictor for the discontinuation of ustekinumab (hazard ratio [HR], 9.696; 95% CI, 4.088~22.998). Competing risk regression analysis modeling of discontinuation because of factors other than satisfaction of an event also revealed that ustekinumab treatment at the patient's expense (HR, 4.138; 95% CI, 1.684~10.168) was a predictor of discontinuation rather than satisfaction. Conclusion: The results of our study revealed that the cost of biologics treatment affects the drug survival of ustekinumab and suggested that economic factors affect the drug survival of ustekinumab treatment in Korea.