Antibody–drug conjugates and bispecific antibodies targeting cancers: applications of click chemistry

Yeji Hong,Su‑Min Nam,Aree Moon 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.3

Engineering approaches using antibody drug conjugates (ADCs) and bispecific antibodies (bsAbs) are designed to overcome the limitations of conventional chemotherapies and therapeutic antibodies such as drug resistance and non-specific toxicity. Cancer immunotherapies have been shown to be clinically successful with checkpoint blockade and chimeric antigen receptor T cell therapy; however, overactive immune systems still represent a major problem. Given the complexity of a tumor environment, it would be advantageous to have a strategy targeting two or more molecules. We highlight the necessity and importance of a multi-target platform strategy against cancer. Approximately 400 ADCs and over 200 bsAbs are currently being clinically developed for several indications, with promising signs of therapeutic activity. ADCs include antibodies that recognize tumor antigens, linkers that stably connect drugs, and powerful cytotoxic drugs, also known as payloads. ADCs have direct therapeutic effects by targeting cancers with a strong payload. Another type of drug that uses antibodies are bsAbs, targeting two antigens by linking to antigen recognition sites or bridging cytotoxic immune cells to tumor cells, resulting in cancer immunotherapy. Three bsAbs and one ADC have been approved for use by the FDA and the EMA in 2022. Among these, two of the bsAbs and the one ADC are used for cancers. We introduced that bsADC, a combination of ADC and bsAbs, has yet to be approved and several candidates are in the early stages of clinical development in this review. bsADCs technology helps increase the specificity of ADCs or the internalization and killing ability of bsAbs. We also briefly discuss the application of click chemistry in the efficient development of ADCs and bsAbs as a conjugation strategy. The present review summarizes the ADCs, bsAbs, and bsADCs that have been approved for anti-cancer or currently in development. These strategies selectively deliver drugs to malignant tumor cells and can be used as therapeutic approaches for various types of cancer.

활성단층으로부터의 안전거리 결정과 규제: 해외사례의 고찰을 바탕으로 한 제언

홍예지(Yeji Hong),김영석(Young-Seog Kim) 대한지질학회 2021 대한지질학회 학술대회 Vol.2021 No.10

최근 우리나라에 두 차례의 중규모 지진(2016년 경주지진, ML=5.8; 2017년 포항지진, MW=5.4)이 발생하면서 피해지진이 발생할 수 있는 활성단층에 대한 조사의 중요성이 대두되었다. 지진이 발생하면 지진동, 액상화, 지표파열 등 여러 가지 지진피해가 발생할 수 있는데, 그 중 지표파열에 의한 재해는 현재까지의 내진기술로는 막을 수 없으며, 좁은 지역에 큰 에너지가 집중되어 심각한 피해가 발생할 수 있다. 지표파열은 주로 기존 활성단층의 재활성화로 인해 발생하며, 일반적으로 새로운 단층과 단열의 생성은 재활성화된 기존 단층의 근처로만 국한되므로 활성단층지도 제작을 통해 기존 활성단층의 위치를 파악하는 것이 선행되어야 한다. 그러나 활성단층지도가 제작된다 하더라도 확실한 기준이나 근거가 없다면 국가에서 실제적으로 이를 어떻게 활용하고 건축물의 건축규제 등에 적용할 것인가 하는 것은 매우 어렵고 민감한 문제이다. 따라서 우리나라에서는 현재 활성단층지도 제작이 이루어지고 있기 때문에 이 논문에서는 활성단층지도가 제작된 이후 활성단층 주변의 규제구역 범위를 어떻게 설정할 것인가에 대해 해외사례를 바탕으로 제안하고자 한다. 이 논문에서는 주로 지질학적 관점에서의 안전성을 고려한 규제거리에 초점을 맞추어 논의하고자 한다. 이러한 안전거리 설정을 위해서는 야외 조사, 단층 종류, 주변 암석의 종류, 예상 지진 규모 등 지표파열 범위 설정을 위한 다양한 요소들을 고려하여 한다. 그러나 우리나라의 경우 지진 발생 주기가 길고 규모가 상대적으로 작기 때문에 이러한 사례가 부족하여 미국, 뉴질랜드, 이탈리아 등 지진재해연구 선진국들의 사례를 바탕으로 고찰하여 지표파열재해로부터의 안전성을 확보하기 위한 우리나라에 적합한 방안을 제안하였다. 해외의 규정을 참고하면 단층자취로부터 양쪽이 대칭이라고 가정할 경우 지표파열이 발생할 수 있는 거리는 단층으로부터 최소 60~200 m, 후퇴거리는 15~20 m를 고려하고 있다. 그러나 이러한 규정이 대부분 지진의 활동성이 높은 지역을 바탕으로 헸다는 것을 고려하면 우리나라에서는 지표파열이 발생할 수 있는 거리를 약 60 m로 하고 이에 대해서는 내진보강과 지질조사를 권고하고, 원전시설을 제외한 신규 건축물의 실질적인 규제에는 안전거리 15 m를 최소한의 거리로 확보하도록 하여 적용할 것을 제안한다. 그러나 실질적인 규정의 적용에 있어서는 건물의 중요도가 높을수록 단층으로부터 더 멀리 위치시키거나 내진기준을 강화하여 건축물의 성격에 따라 탄력적인 적용을 하는 것이 국민의 불편을 최소화하고 안전을 확보하는 현실적인 방안일 것으로 판단된다.

빌딩 정보 모델을 이용한 실내 장면의 이해

홍예지(Hong, Yeji),박소민(Park, Somin),김형관(Kim, Hyoungkwan) 대한토목학회 2020 대한토목학회 학술대회 Vol.2020 No.10

건설 현장 작업자 안전 관리를 위한 도메인 적응형 의미적 분할

홍예지(Hong, Yeji),천웨이치(Chern, Wei Chih),누웬탐반(Nguyen, Tam Van),김홍조(Kim, Hongjo) 대한토목학회 2021 대한토목학회 학술대회 Vol.2021 No.10

아두이노 기반의 실내외 미세먼지 파악 서비스 연구

홍예지 ( Yeji Hong ),박동희 ( Donghee Park ),공민정 ( Minjeong Kong ) 한국정보처리학회 2022 한국정보처리학회 학술대회논문집 Vol.29 No.2

인체의 미세먼지 노출에 의한 연구가 활발히 진행되면서 미세먼지와 건강 영향에 대한 인과 관계가 입증되고 있다. 미세먼지는 기침, 재채기, 심혈관 질환, 폐암 등 가벼운 증상부터 심각한 질병까지 인체의 건강에 다양하게 영향을 미칠 수 있다. 미세먼지는 2000 년 초부터 꾸준히 높은 농도를 보여왔지만, 사람들이 실제로 미세먼지를 위험 물질로 인식하기 시작한 것은 10 년이 채 되지 않았다. 이에 본 논문은 실외 미세먼지에 대한 정보 제공뿐만 아니라 사용자가 실제로 위치한 실내 미세먼지 농도까지 함께 제공하여 미세먼지에 관한 관심을 증가시키고자 한다.

양산단층 단구리 트렌치의 위변위와 단층조선을 이용한 지진규모산정

홍예지(Yeji Hong),이진현(Jinhyun Lee),Sowreh Rezaei,김영석(Young-Seog Kim) 대한지질학회 2015 대한지질학회 학술대회 Vol.2015 No.10

Prolonged Limb and Respiratory Muscle Weakness Associated with Japanese Encephalitis Virus Infection: A Case Report

Hong Sunmok,Park Seoyeong,Lee Yeji,Lee Ryeojin,Hyun Sung Eun 대한근전도전기진단의학회 2023 대한근전도 전기진단의학회지 Vol.25 No.1

Patients diagnosed with Japanese encephalitis (JE) may present with flaccid paralysis. JE has also been reported to be accompanied by anterior horn cell disease or motor axonal polyneuropathy. We report a case of a patient with JE with prolonged limb and respiratory muscle weakness who underwent electrodiagnostic studies, including a phrenic nerve conduction study, 10 months after the onset of paralysis. During that 10-month period, severe weakness of the upper and lower extremities showed no recovery, and the patient required long-term ventilator support through a tracheostomy. Nerve conduction studies and electromyography revealed chronic anterior horn cell disease with abundant denervation potentials involving the craniobulbar, cervical, thoracic, and lumbosacral segments. In addition to the nerves in the upper and lower extremities, the phrenic motor nerves showed abnormalities indicative of diaphragmatic weakness. Therefore, in patients with JE with chronic limb weakness and respiratory difficulty, thorough electrodiagnostic studies should be performed to diagnose the combination of anterior horn cell disease with encephalitis and to evaluate the condition’s severity and prognosis.

Relationship between seafood consumption and bisphenol A exposure: the Second Korean National Environmental Health Survey (KoNEHS 2012–2014)

Yeji Kim,Minkyu Park,Do Jin Nam,Eun Hye Yang,Jae-Hong Ryoo 대한직업환경의학회 2020 대한직업환경의학회지 Vol.32 No.-

Background: This study aimed to identify the relationship between exposure to bisphenol A (BPA) and seafood consumption using a nationally representative data of the general Korean population. Methods: This study was conducted on 5,402 adults aged 19 years and older (2,488 men, 2,914 women) based on the second Korean National Environmental Health Survey (2012–2014). We stratified the data according to gender and analyzed urinary BPA concentrations in terms of sociodemographic characteristics, health behavior, dietary factor, and seafood consumption. In the high and low BPA exposure groups, the odds ratios (ORs) were calculated using logistic regression analysis according to the top 75th percentile concentration. Results: In men, large fish and tuna and other seafood categories had significantly higher ORs before and after adjustment in the group who consumed seafood more than once a week than in the group who rarely consumed seafood, with an adjusted value of 1.97 (95% confidence interval [CI]: 1.12–3.48) and 1.74 (95% CI: 1.10–2.75), respectively. In the shellfish category, the unadjusted OR was 1.61 (95% CI: 1.00–2.59), which was significantly higher in the group who consumed seafood more than once a week than in the group who rarely consumed seafood. However, the OR after adjusting for the variables was not statistically significant. In women, the frequency of seafood consumption and the concentration of urinary BPA were not significantly associated. Conclusions: BPA concentration was higher in men who frequently consumed large fish and tuna, shellfish and other seafood in this study.

Quality Characteristics of Kimchi Fermented with Biogenic Amine-reducing Bacteria

Yeji PARK,Woo Hong JOO 한국생물공학회 2018 한국생물공학회 학술대회 Vol.2018 No.10

Transient Plant Expression of Recombinant Rabies Virus Glycoprotein: A strategy for Vaccine Production

Lee Yeji,Park Jeanho,Kim Yerin,Hwang Hyunjoo,Jin Caiquan,Oh Yoojin,Kang Yangjoo,Lee Daehwan,Song Minhyeok,Lee Yoonji,고기성,Hong Mineui 한국원예학회 2024 원예과학기술지 Vol.42 No.3

The rabies virus causes neurological infections, resulting in the deaths of over 60,000 people worldwide each year. Currently available rabies vaccines are attenuated virus vaccines, which carry the risk of transmission among both humans and animals. An exciting alternative to these traditional vaccines is the use of recombinant plant-based vaccines. In this study, we applied the rabies virus glycoprotein (RVGP) as a recombinant vaccine to be transiently expressed in plants. To achieve this, we fused human immunoglobulin G Fc with the KDEL sequence, a motif for endoplasmic reticulum (ER) retention (FcK), to the RVGP, to generate RVGP-FcK. We then cloned the RVGPFcK gene expression cassette into the pEAQ vector and agro-infiltrated Agrobacterium tumefaciens (LBA4404) carrying the pEAQ RVGP-FcK vector into the leaves of Nicotiana benthamiana for transient expression. A RT-PCR analysis confirmed the transcription of the RVGP-FcK gene, which was evident as early as four days post-infiltration (dpi). To optimize the spatial and temporal aspects of RVGP-FcK production, we conducted analyses of its expression levels at different leaf positions (top, middle, and base) and dpi. A western blot analysis demonstrated that the RVGP-FcK protein reached its highest expression level at 7 dpi in the top leaf position and at 5 dpi in the middle leaf position. However, no detectable expression was observed in the bottom leaves at any time point. Subsequently, we validated the functionality of RVGP-FcK through an ELISA analysis. The results revealed that RVGP-FcK was expressed and assembled into its functional form most effectively at 5 and 7 dpi in the top leaf position and at 5 and 7 dpi in the middle leaf position. Our findings demonstrate that the transient expression of a functional RVGP-FcK protein can be optimized spatially and temporally in plants.