Affinity Maturation of Monoclonal Antibody 1E11 by Targeted Randomization in CDR3 Regions Optimizes Therapeutic Antibody Targeting of HER2-Positive Gastric Cancer

AbstractIt 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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Drug-induced thrombocytopenia associated with trastuzumab in a patient with HER2-positive recurrent gastric cancer

International Cancer Conference Journal ◽

10.1007/s13691-021-00520-z ◽

2021 ◽

Author(s):

Yuko Takano ◽

Satoshi Furune ◽

Yuki Miyai ◽

Sachi Morita ◽

Megumi Inoue ◽

...

Keyword(s):

Gastric Cancer ◽

Monoclonal Antibody ◽

Bone Marrow ◽

Elevated Level ◽

Oral Prednisolone ◽

Severe Thrombocytopenia ◽

Her2 Positive ◽

Drug Induced ◽

Recurrent Gastric Cancer ◽

Positive Recurrent

AbstractHere, we report a 57-year-old female patient with HER2-positive recurrent gastric cancer who experienced drug-induced thrombocytopenia associated with trastuzumab, a humanized anti-HER2 monoclonal antibody. Shortly after the initiation of S-1, oxaliplatin, and trastuzumab chemotherapy, the patient experienced severe thrombocytopenia and did not respond to platelet transfusions. Based on the findings of increased numbers of polynuclear megakaryocytes in the bone marrow and an elevated level of platelet-associated IgG (PA-IgG), the patient was diagnosed with drug-induced thrombocytopenia (DITP). The platelet count recovered rapidly with oral prednisolone (1 mg/kg). Since we initially suspected oxaliplatin as the causal agent, S-1 was restarted as a monotherapy, followed by trastuzumab after a 3-week interval, without oxaliplatin. On the second day after the addition of trastuzumab, severe thrombocytopenia occurred again, which suggests that trastuzumab was responsible for the DITP. The patient no longer experienced severe thrombocytopenia during the subsequent S-1 and oxaliplatin chemotherapy, which supports this hypothesis.

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Sa1928 A Humanization and Affinity Maturation of an Anti-CD24 Monoclonal Antibody Targeting Gastrointestinal Cancers

Gastroenterology ◽

10.1016/s0016-5085(15)31202-6 ◽

2015 ◽

Vol 148 (4) ◽

pp. S-357

Author(s):

Shiran Shapira ◽

Dina Kazanov ◽

Sarah Kraus ◽

Itai Benhar ◽

Nadir Arber

Keyword(s):

Monoclonal Antibody ◽

Affinity Maturation ◽

Gastrointestinal Cancers ◽

Antibody Targeting

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HER2 Expression in Gastric Cancer and Gastroesophageal Junction Cancer

Journal of Surgical Sciences ◽

10.3329/jss.v22i2.44069 ◽

2020 ◽

Vol 22 (2) ◽

pp. 79-82

Author(s):

Md Azizur Rahman ◽

Abdullah Md Abu Ayub Ansari ◽

Kazi Mazharul Islam ◽

Md Aminur Rahman ◽

ABM Abdul Matin ◽

...

Keyword(s):

Gastric Cancer ◽

Gastric Carcinoma ◽

Social Impact ◽

Gastroesophageal Junction ◽

Treatment Protocol ◽

Armed Forces ◽

Her2 Expression ◽

Her2 Positive ◽

Cancer Data ◽

Her2 Positivity

Background: Carcinoma of the stomach is a major cause of cancer mortality worldwide. Due to social impact of gastric carcinoma (GC), there is a need to stratify patients into appropriate screening, surveillance and treatment programs. Although histopathology remains the most reliable and less expensive method, numerous efforts have been made to identify and validate novel biomarkers to accomplish the goals. In recent years, several molecules have been identified and tested for their clinical relevace in GC management. Among the biomarkers with the exception of HER2, none of the biomarkers is currently used in clinical practice, and some of them were described in single studies. Materials and Methods: This prospective type of observational study was performed in the Department of Surgery, Dhaka Medical College Hospital, Dhaka, 6 months from approval of protocol. Total 45 consecutive patients aged 18 years and above without consideration of gender were selected purposefully. Every patient was evaluated by clinical examination, appropriate investigations and after a confirm diagnosis of the tissue from the cancer. All patients have undergone operative intervention and Gastrectomy specimens were subtotal (including cardiac and pylorus), subtotal (including the pylorus), total radical gastrectomy and oesophago-gastrectomy sample. All specimens obtained were immersed in 10% formalin. Samples of whom were sent to the department of pathology, DMCH for histopathology examination. Portion of representative tissue/block was sent to AFIP (Armed Forces Institute of Pathology, Dhaka) for immunohistochemistry to find out the HER2 expression in gastric cancer and gastro-oesophageal cancer. Data was collected in a pre-designed questionnaire by face to face interview. Result and observation: In this study when 45 cases were categorized according to WHO grading system it was observed that majority (30) patients were found in grade II, among them 3(10%) were HER2 positive. But with grade III tumour the HER2 positivity were found more i,e; 37.5% (3/8). Grade- I tumor show HER2 neu expression 28.57% (2/7) and according to location most of the cases with HER2 positive expression was located in the gastro-esophageal junction which is 27.27% (3/11) than gastric carcinoma which is 14.70% (5/34). Conclusion: Most of the patients of gastric and gastrooesophageal junction adenocarcinoma are diagnosed at a very late stage, so they require special attention in treatment protocol, including chemotherapy and immunotherapy for increasing their survivability. The study showed with poorly differentiated (high grade) tumour, the HER2 positivity were found more. Journal of Surgical Sciences (2018) Vol. 22 (2) : 79-82

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Efficacy of bezlotoxumab, the monoclonal antibody targeting C. difficile toxin B, for prevention of C. difficile infection (CDI) recurrence in patients at high risk of recurrence or CDI-related adverse outcomes

10.26226/morressier.56d5ba27d462b80296c95f82 ◽

2016 ◽

Author(s):

Dale N. Gerding

Keyword(s):

Monoclonal Antibody ◽

High Risk ◽

Adverse Outcomes ◽

Toxin B ◽

Risk Of Recurrence ◽

Antibody Targeting

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DS-8201a in HER2-positive Gastric Cancer That Cannot Be Surgically Removed or Has Spread

Case Medical Research ◽

10.31525/ct1-nct04014075 ◽

2019 ◽

Author(s):

Keyword(s):

Gastric Cancer ◽

Her2 Positive

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Trastuzumab-based palliative chemotherapy for HER2-positive gastric cancer: a single-center real-world data

BMC Cancer ◽

10.1186/s12885-021-08058-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Tae-Hwan Kim ◽

Hun Do Cho ◽

Yong Won Choi ◽

Hyun Woo Lee ◽

Seok Yun Kang ◽

...

Keyword(s):

Gastric Cancer ◽

Real World ◽

Group Performance ◽

Eastern Cooperative Oncology Group ◽

Conversion Surgery ◽

Single Center ◽

Her2 Positive ◽

Real World Data ◽

World Data ◽

The Real

Abstract Background Since the results of the ToGA trial were published, trastuzumab-based chemotherapy has been used as the standard first-line treatment for HER2-positive recurrent or primary metastatic gastric cancer (RPMGC). However, the real-world data has been rarely reported. Therefore, we investigated the outcomes of trastuzumab-based chemotherapy in a single center. Methods This study analyzed the real-world data of 47 patients with HER2-positive RPMGC treated with trastuzumab-based chemotherapy in a single institution. Results With the median follow-up duration of 18.8 months in survivors, the median overall survival (OS) and progression-free survival were 12.8 and 6.9 months, respectively, and the overall response rate was 64%. Eastern Cooperative Oncology Group performance status 2 and massive amount of ascites were independent poor prognostic factors for OS, while surgical resection before or after chemotherapy was associated with favorable OS, in multivariate analysis. In addition, 5 patients who underwent conversion surgery after chemotherapy demonstrated an encouraging median OS of 30.8 months, all with R0 resection. Conclusions Trastuzumab-based chemotherapy in patients with HER2-positive RPMGC in the real world demonstrated outcomes almost comparable to those of the ToGA trial. Moreover, conversion surgery can be actively considered in fit patients with a favorable response after trastuzumab-based chemotherapy.

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