Adverse events to monoclonal antibodies used for cancer therapy: Focus on hypersensitivity responses

Baldo, Brian A.

doi:10.4161/onci.26333

Cited by 163 publications

(144 citation statements)

References 128 publications

Supporting

Mentioning

137

Contrasting

Unclassified

Order By: Relevance

“…Activation of complement pathway, antibody-dependent cytotoxity and cell apoptosis are other potential mechanisms of action, already known from other anti-CD20 MoAbs [39]. Infusional reactions are similar to those seen with naked MoAbs.…”

Section: Yttrium-90 Ibritumomab Tiuxetanmentioning

confidence: 63%

“…In radioimmunotherapy, the anti-CD20 MoAbs lead to direct cell apoptosis through the radioactive portion of their molecule [39]. Activation of complement pathway, antibody-dependent cytotoxity and cell apoptosis are other potential mechanisms of action, already known from other anti-CD20 MoAbs [39].…”

Section: Yttrium-90 Ibritumomab Tiuxetanmentioning

confidence: 99%

“…Within the cell, MMAE is released and binds to tubulin. Disruption of microtubule network induces cell cycle arrest and apoptosis of CD30-expressing tumor cell [39], [50]. Brentuximab is licensed for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin's lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL) [51].…”

Section: Brentuximab Vedotinmentioning

confidence: 99%

See 2 more Smart Citations

Immediate Reactions To Monoclonal Antibodies In Clinical Hematology

Kyriazi

2016

IJMS

View full text Add to dashboard Cite

Monoclonal antibodies (MoAbs) have been widely used in clinical hematology. As foreign macro-molecules, they can cause infusional reactions during the administration or within 24 hours after the infusion, which encompass a spectrum of mechanisms. Although most of these reactions are non-allergic, are often indistinguishable from true allergic reactions mediated by IgE immunoglobulins. The diagnosis is often challenging and relies mainly on clinical criteria. They occur during the first doses, soon after the initiation of treatment. The symptoms are usually well controlled by the immediate drug discontinuation or reduction of the infusion rate. The management remains largely supportive, consisting of oxygen, intravenous fluids, bronchodilators, antihistamines and steroids. Most of MoAb protocols recommend premedication with steroids and antihistamines and gradually escalating infusion rates. Increased medical and nursing vigilance is required and resuscitative equipment should always be readily available. These events affect patients' quality of life, leading to treatment delay or discontinuation and series of tests. The decision to rechallenge the treatment depends on severity grading, clinical parameters and treatment goals. This article provides an update of MoAbs used in clinical hematology. It summarizes the pathophysiology, the diagnostic approach, the preventive measures and treatment of MoAb-related reactions.

show abstract

Section: Yttrium-90 Ibritumomab Tiuxetanmentioning

confidence: 63%

Section: Yttrium-90 Ibritumomab Tiuxetanmentioning

confidence: 99%

Section: Brentuximab Vedotinmentioning

confidence: 99%

See 1 more Smart Citation

Immediate Reactions To Monoclonal Antibodies In Clinical Hematology

Kyriazi

2016

IJMS

View full text Add to dashboard Cite

show abstract

“…Liver toxicity is less commonly observed with biologics agents than with small molecule chemotherapy agents (Baldo, 2013;Saez et al, 2012). A notable exception is the TNF Receptor Super Family (TNFRSF), where agonist antibodies to multiple TNFRSF members have been found to induce liver toxicity with a range of incidence and severity.…”

Section: Discussionmentioning

confidence: 99%

Modeling Hepatocellular Toxicity of Enavatuzumab, a Humanized Anti-TweakR Antibody

Choi¹,

Zhu

Chao³

et al. 2017

American Journal of Pharmacology and Toxicology

View full text Add to dashboard Cite

Abstract:In a Phase 1 clinical study, treatment with enavatuzumab, a humanized monoclonal antibody to TweakR, resulted in liver toxicity in a subset of patients. The objective of this current study was to evaluate the ability of preclinical studies to predict liver toxicity in humans. Enavatuzumab was evaluated in cynomolgus monkeys, where serum liver enzyme and cytokine levels were measured and histopathology of the liver was performed. TweakR expression was evaluated by immunohistochemistry in healthy human liver and in liver tissues from cancer patients. Enavatuzumab was also evaluated in vitro for its impact on human hepatocytes when cultured both alone and with immune cells. Enavatuzumab-treated cynomolgus monkeys exhibited liver enzyme elevations only at the highest dose level (100 mg/kg) and few cytokines were elevated after dosing. Bile duct hyperplasia was observed in the liver but appeared to be partially reversible. Compared with healthy liver, liver tissues from cancer patients exhibited marked elevation of TweakR expression, which was associated with immune cell infiltration. Enavatuzumab treatment of cultured hepatocytes, both in the presence and absence of immune cells resulted in increased cytokine release, but only in the co-cultures were liver enzymes elevated. These results suggest that due to differences in liver architecture between healthy humans and cancer patients, studies in healthy non-human primates may underestimate the potential for liver toxicity in human cancer patients. The use of additional in vitro assays in conjunction with in vivo studies may better predict the potential impact of a therapeutic agent on the liver in clinical studies.

show abstract

“…crosslinking Fc receptors, which may lead to injection site reactions. Immediate type reactions occur for nearly all authorized monoclonal antibodies, but these have mostly not been associated with the presence of ADA [19]. A notable exception is cetuximab, where pre-existing anti-galactose-α-1, 3-galactose IgE antibodies have been linked to the occurrence of HSR's.…”

Section: Residual Safety Concerns At Time Of Authorization That May Pmentioning

confidence: 99%

Interchangeability. An insurmountable fifth hurdle?

Ebbers¹,

Chamberlain²

2014

GaBI J

View full text Add to dashboard Cite

The arrival of biosimilars has led to considerable debate on how they can be used in clinical practice. A particular concern is related to the question of whether a biosimilar can be safely interchanged with the originator product or other biosimilars. Here we will discuss challenges to the regulatory approach for establishing interchangeability, in the sense of considering biosimilar versions as therapeutic equivalents that could -depending on National or Federal Law -be substituted at the pharmacy level, and compare these to the weight of real-world evidence of the risks of potential diff erences that could modify longer-term clinical benefi t-to-risk. Our discussion will be mainly focused on monoclonal antibodies. We conclude that it will be highly challenging to establish interchangeability of biosimilars, and it should be questioned whether the 'higher' standard required for designation of interchangeability adds to the benefi t for patients.

show abstract

Adverse events to monoclonal antibodies used for cancer therapy: Focus on hypersensitivity responses

Cited by 163 publications

References 128 publications

Immediate Reactions To Monoclonal Antibodies In Clinical Hematology

Immediate Reactions To Monoclonal Antibodies In Clinical Hematology

Modeling Hepatocellular Toxicity of Enavatuzumab, a Humanized Anti-TweakR Antibody

Interchangeability. An insurmountable fifth hurdle?

Contact Info

Product

Resources

About