• Journal of Life Science
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• v.19 no.1
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• pp.123-128
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• 2009

Production of highly valuable immunotherapeutic proteins such as monoclonal antibodies and vaccines using plant biotechnology and genetic engineering has been studied as a popular research field. Plant expression system for mass production of such useful recombinant therapeutic proteins has several advantages over other existing expression systems with economical and safety issues. Immunotherapy of multiple monoclonal antibodies, which can recognize multiple targeting including specific proteins and their glycans highly expressed on the surface of cancer cells, can be an efficient treatment compared to a single targeting immunotherapy using a single antibody. In this study, we have established plant production system to express two different targeting monoclonal antibodies in a single transgenic plant through crossing fertilization between two different transgenic plants expressing anti-colorectal cancer mAbCO17-1A and anti-breast cancer mAbBR55, respectively. The F1 seedlings were obtained cross fertilization between the two transgenic parental plants. The presence, transcription, and protein expression of heavy chain (HC) and light chain (LC) genes of both mAbs in the seedlings were investigated by PCR, RT-PCR, and immunoblot analyses, respectively. Among all the seedlings, some seedlings did not carry or transcribe the HC and LC genes of both mAbs. Thus, the seedlings with presence and transcription of HC and LC genes of both mAbs were selected, and the selected seedlings were confirmed to have relatively stronger density of HC and LC protein bands compared to the transgenic plant expressing only each mAb. These results indicate that the F1 seedling plant with carrying both mAb genes was established. Taken together, plant crossing fertilization can be applied to generate an efficient production system expressing multiple monoclonal antibodies for immunotherapy in a single plant.

• Journal of Korean Medical Science
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• v.33 no.52
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• pp.346.1-346.11
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• 2018

Background: To evaluate the therapeutic benefits of the treat-to-target (T2T) strategy for Asian patients with early rheumatoid arthritis (RA) in Korea. Methods: In a 1-year, multicenter, open-label strategy trial, 346 patients with early RA were recruited from 20 institutions across Korea and stratified into 2 groups, depending on whether they were recruited by rheumatologists who have adopted the T2T strategy (T2T group) or by rheumatologists who provided usual care (non-T2T group). Data regarding demographics, rheumatoid factor titer, anti-cyclic citrullinated peptide antibody titer, disease activity score of 28 joints (DAS28), and Korean Health Assessment Questionnaire (KHAQ) score were obtained at baseline and after 1 year of treatment. In the T2T group, the prescription for disease-modifying antirheumatic drugs was tailored to the predefined treatment target in each patient, namely remission (DAS28 < 2.6) or low disease activity (LDA) ($2.6{\leq}DAS28$ < 3.2). Results: Data were available for 163 T2T patients and 162 non-T2T patients. At the end of the study period, clinical outcomes were better in the T2T group than in the non-T2T group (LDA or remission, 59.5% vs. 35.8%; P < 0.001; remission, 43.6% vs. 19.8%; P < 0.001). Compared with non-T2T, T2T was also associated with higher rate of good European League Against Rheumatism response (63.0% vs. 39.8%; P < 0.001), improved KHAQ scores (-0.38 vs. -0.13; P = 0.008), and higher frequency of follow-up visits (5.0 vs. 2.0 visits/year; P < 0.001). Conclusion: In Asian patients with early RA, T2T improves disease activity and physical function. Setting a pre-defined treatment target in terms of DAS28 is recommended.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.2 no.2
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• pp.169-177
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• 1999

Purpose: To evaluate the efficacy of interferon alpha therapy with or without prednisolone in children with chronic hepatitis B. Methods: Twenty-eight children (22 boys, 6 girls, mean age 130 months) had seropositive results for HBsAg, HBeAg and HBV DNA; 11 had chronic persistent hepatitis and 17 had chronic active hepatitis. The patients were divided into two groups depending upon their inflammatory activity on liver biopsy, pretreatment serum ALT levels and HBV DNA levels. Fourteen children (group 1: chronic active hepatitis, ALT ${\geq}$ 100 IU/L and HBV DNA ${\leq}$ 100 pg/$300\;{\mu}L$) received interferon alpha 2a 5 $MU/m^2$ of body surface three times weekly for 6 months. Fourteen children (group 2: chronic persistent hepatitis or chronic active hepatitis with ALT < 100 IU/L or HBV DNA > 100 pg/$300\;{\mu}L$) received prednisolone in decreasing daily doses of 60 mg/$m^2$, 40 mg/$m^2$, and 20 mg/$m^2$, each for 2 weeks, followed after 2 weeks by interferon alpha 2a on the same schedule. At the end of therapy, 3 end points were analyzed: HBeAg seroconversion, serum ALT normalization rate and clearance of serum HBV DNA. Results: At the end of treatment, HBe antigen-to antibody seroconversion was higher but not more significant in group 1 than group 2 (71.4% vs. 50.0%). Only one patient in group 2 who lost HBeAg, also cleared HBsAg. ALT normalization was similar in both groups (64.3% in group 1 vs. 55.6% in group 2). Clearance of serum HBV DNA was observed in 78.6% of patients in group 1 and 64.3% in group 2, but no significant differences. Complete response was similarly achieved in both groups (57.1% in group 1 vs. 50.0% in group 2). Interferon alpha therapy with prednisolone priming was well tolerated and all children finished therapy. Conclusion: The combined therapy with prednisolone followed by interferon alpha may be safe and effective in inducing a serological and biochemical remission of the disease in approximately 50% of children with chronic hepatitis B and with a high level of viral replication and less active disease. However, a controlled study should be performed to confirm these results.