Pre-existing antitherapeutic antibodies against the Fc region of the hu14.18K322A mAb are associated with outcome in patients with relapsed neuroblastoma

PurposePatients with cancer receiving tumor-reactive humanized monoclonal antibody (mAb) therapy can develop a human antihuman antibody (HAHA) response against the therapeutic mAb. We evaluated for HAHA in patients with neuroblastoma treated in a phase I study of humanized anti-GD2 mAb (immunoglobulin (Ig)G1 isotype), hu14.18K322A (NCT00743496). The pretreatment sera (collected prior to mAb treatment) from 9 of 38 patients contained antitherapeutic antibodies, even though they had no prior mAb exposure. We sought to characterize these pre-existing antitherapeutic antibodies (PATA).Experimental designThe PATA+ pretreatment samples were characterized via ELISA; clinical associations with PATA status were evaluated.ResultsPretreatment sera from eight of nine PATA+ patients also bound rituximab and demonstrated preferential ELISA reactivity against the Fc portions of hu14.18K322A and rituximab as compared with the Fab portions of these mAbs. These PATA+ sera also recognized dinutuximab (human IgG1 isotype) and mouse IgG2a isotype mAbs, but not a mouse IgG1 isotype or the fully human panitumumab (IgG2 isotype) mAb. Of the 38 treated patients, only 4 patients (all in the PATA+ cohort) demonstrated no disease progression for>2.5 years without receiving further therapy (p=0.002).ConclusionsThis study demonstrates an association between clinical outcome and the presence of PATA against determinant(s) on the Fc component of the therapeutic mAb, suggesting that the PATA may be playing a role in augmenting mAb-based antitumor effects. Further analyses for the presence of PATA in a larger cohort of patients with relapsed neuroblastoma, analyses of their clinical correlates, identification of their immunological targets, and potential antitumor mechanisms are warranted.

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Development of humanized rabbit monoclonal antibodies against vascular endothelial growth factor receptor 2 with potential antitumor effects

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2013.06.007 ◽

2013 ◽

Vol 436 (3) ◽

pp. 543-550 ◽

Cited By ~ 9

Author(s):

Yanlan Yu ◽

Pierre Lee ◽

Yaohuang Ke ◽

Yongke Zhang ◽

Jungang Chen ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Monoclonal Antibodies ◽

Growth Factor ◽

Growth Factor Receptor ◽

Vascular Endothelial ◽

Antitumor Effects ◽

Endothelial Growth Factor ◽

Potential Antitumor

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Effect of Sucrose on Cisplatin-induced Fatigue-like Behavior in Mice: Comparison With Fructose and Glucose

Cancer Diagnosis & Prognosis ◽

10.21873/cdp.10014 ◽

2021 ◽

Vol 1 (2) ◽

pp. 95-102

Author(s):

KAZUMI YOSHIZAWA ◽

RUKA KURONO ◽

HARUKA SATO ◽

ERIKA ISHIJIMA ◽

HARUKA NASU ◽

...

Keyword(s):

Tumor Growth ◽

Anticancer Agents ◽

Saline Control ◽

Common Symptom ◽

Antitumor Effects ◽

Patients With Cancer ◽

Cancer Related Fatigue ◽

Running Activity ◽

Glucose Intake

Background/Aim: Fatigue is the most common symptom in patients with cancer undergoing radiation therapy or cancer chemotherapy. However, cancer-related fatigue remains undertreated and poorly understood. Materials and Methods: Mice were administered a single dose of cisplatin (10 mg/kg, intraperitoneally) or saline (as a control) and then treated with sucrose, fructose, glucose (each at 500 or 5,000 mg/kg, orally), or saline (control) daily for 4 days. cisplatin-induced fatigue-like behavior was investigated by assessment of running activity on a treadmill. The influence of glucose intake on tumor growth was also examined in Lewis lung carcinoma (LLC)-bearing mice. Results: Administration of sucrose and glucose improved cisplatin-induced fatigue-like behavior in mice, whereas administration of fructose showed only slight antifatigue effects. Although glucose-fed mice showed increased tumor growth, this was balanced out by the powerful cytotoxicity of cisplatin. Conclusion: Sucrose, and especially glucose, may improve patient quality of life during treatment with anticancer agents by preventing fatigue without interfering with the antitumor effects of cisplatin.

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Blocking Tics in Gilles de la Tourette Syndrome

Frontiers in Neurology ◽

10.3389/fneur.2021.686785 ◽

2021 ◽

Vol 12 ◽

Author(s):

Justyna Kaczyńska ◽

Piotr Janik

Keyword(s):

Obsessive Compulsive Disorder ◽

Tourette Syndrome ◽

Age Of Onset ◽

Severe Form ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Clinical Correlates ◽

Clinical Associations ◽

Motor Acts

Introduction: Patients with Gilles de la Tourette syndrome (GTS) may experience blocking tics (BTs) defined as recurrent, brief cessations of motor acts. The aim of this study was to assess the prevalence, age of onset, and clinical correlates of BTs in GTS patients.Materials and Methods: We performed a one-time registration study in a cohort of 195 consecutive GTS patients aged 5–66 years (mean age: 15.0 ± 9.2; 47 females, 24.1%). All patients were personally interviewed and examined.Results: At least one BT occurred at some point in the lifetime of 73 patients (37.4%) with a mean age of onset of 10.4 ± 5.9 years. BTs occurred an average of 4.8 ± 5.3 years after tic onset. The most common BT was cessation of walking (n = 59, 80.8%), followed by speech (n = 19, 26.0%), running (n = 18, 24.7%), and writing (n = 9, 12.3%). Most of the patients (n = 52, 71.2%) reported cessation of only one activity. Clinical associations of BTs included more severe tics, overall greater number of tics, and, to a lesser extent, higher age at evaluation and comorbid obsessive-compulsive disorder.Conclusions: BTs represent complex tics, early and common symptoms of GTS, and are associated with a more severe form of GTS.

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