Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease

Cobleigh, Melody A.; Vogel, Charles L.; Tripathy, Debasish; Robert, Nicholas J.; Scholl, Susy; Fehrenbacher, Louis; Wolter, Janet; Paton, Virginia; Shak, Steven; Lieberman, G.; Slamon, Dennis J.

doi:10.1200/jco.1999.17.9.2639

Cited by 2,541 publications

(1,506 citation statements)

References 22 publications

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“…These results indicate that HercepTest 3 þ patients in oesophageal SCC will be the best candidates for anti-HER-2 immune targeting. It has already been shown in breast cancer trials that there is a greater benefit from Herceptin therapy for 3 þ patients compared to those who were 2 þ (Cobleigh et al, 1999;Slamon et al, 2001). …”

Section: Discussionmentioning

confidence: 99%

Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma

et al. 2005

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The utilisation of antitumour T cells induced by cancer vaccination with HER-2 peptides or antibodies (Herceptin) against HER-2, as immunotherapy for oesophageal cancer, is a novel and attractive approach. It is important to clarify the frequencies of HER-2 expression and gene amplification in patients with oesophageal squamous cell carcinoma (SCC) and to evaluate the relationship between HER-2 status and HLA haplotype, since the candidates for HER-2 peptide-based vaccination are restricted to a certain HLA haplotype. We determined the frequency of HER-2 expression using the HercepTestt for immunohistochemistry and HER-2 gene amplification by fluorescence in situ hybridisation (FISH) assay in oesophageal SCC (n ¼ 66). HER-2-positive tumours (1 þ /2 þ /3 þ ) analysed by a HercepTest were observed in 30.3% of all the patients and HER-2 gene amplification evaluated by FISH was observed in 11.0% of all the patients, in which all HercepTest (3 þ ) tumours were found to have gene amplification and three of six moderately positive (2 þ ) tumours showed gene amplification. Furthermore, HER-2-positive cells were present more diffusely and were larger within each tumour in the patients who were HercepTest 3 þ than those who were HercepTest 1 þ . Moreover, the survival rate in HER-2-positive group was significantly worse than that in HER-2-negative group. Also, the survival rate in the patients with HER-2 gene amplification was significantly worse than that without HER-2 gene amplification. In addition, oesophageal SCC patients with both HLA-A24-positive and HER-2-positive tumours (1 þ /2 þ /3 þ ) accounted for 26% of these cases, and both HLA-A2-and HER-2-positive tumours accounted for 18% of them.

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Section: Discussionmentioning

confidence: 99%

Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma

et al. 2005

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“…Initial trials showed it was well tolerated and produced durable response in patients who had failed first‐ and second‐line chemotherapy 21, 22, 23. Subsequent large, phase III trials showed significant improvements in time to treatment failure and overall mortality in patients with progressive metastatic breast cancer 5.…”

Section: The Benefits Of Her2 Targeted Therapiesmentioning

confidence: 99%

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

Florido

Smith

Cuomo

et al. 2017

JAHA

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“…Monoclonal antibodies (mAbs) are an important class of biomolecules that are used in the treatment of various diseases such as cancer, multiple sclerosis, rheumatoid arthritis, lupus, and respiratory diseases (Choy et al, 1998; Cobleigh et al, 1999; Haynes et al, 2009; Helliwell and Coles, 2009; Robak and Robak, 2009). During mAb process development, aggregates and fragments have to be removed to adequate levels due to their associated risks with increased immunogenicity and potential effects on drug efficacy (Fan et al, 2012; Rosenberg, 2006).…”

Section: Introductionmentioning

confidence: 99%

Effects of antibody disulfide bond reduction on purification process performance and final drug substance stability

Chung¹,

Russell²,

Yang³

et al. 2017

Biotech & Bioengineering

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Antibody disulfide bond reduction during monoclonal antibody (mAb) production is a phenomenon that has been attributed to the reducing enzymes from CHO cells acting on the mAb during the harvest process. However, the impact of antibody reduction on the downstream purification process has not been studied. During the production of an IgG2 mAb, antibody reduction was observed in the harvested cell culture fluid (HCCF), resulting in high fragment levels. In addition, aggregate levels increased during the low pH treatment step in the purification process. A correlation between the level of free thiol in the HCCF (as a result of antibody reduction) and aggregation during the low pH step was established, wherein higher levels of free thiol in the starting sample resulted in increased levels of aggregates during low pH treatment. The elevated levels of free thiol were not reduced over the course of purification, resulting in carry‐over of high free thiol content into the formulated drug substance. When the drug substance with high free thiols was monitored for product degradation at room temperature and 2–8°C, faster rates of aggregation were observed compared to the drug substance generated from HCCF that was purified immediately after harvest. Further, when antibody reduction mitigations (e.g., chilling, aeration, and addition of cystine) were applied, HCCF could be held for an extended period of time while providing the same product quality/stability as material that had been purified immediately after harvest. Biotechnol. Bioeng. 2017;114: 1264–1274. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals Inc.

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Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease

Cited by 2,541 publications

References 22 publications

Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma

Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

Effects of antibody disulfide bond reduction on purification process performance and final drug substance stability

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