Neurotoxicity of antibodies in cancer therapy: A review

Horta, Erika; Bongiorno, Connie; Ezzeddine, Mustapha A.; Neil, Elizabeth

doi:10.1016/j.clineuro.2019.105566

Cited by 12 publications

(11 citation statements)

References 34 publications

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“…The primary neurologic complication seen among HER2‐targeted therapies is neuropathy, likely related to the concomitant use of taxanes, and management is reviewed below. Overall, with the monoclonal antibodies pertuzumab and trastuzumab, neuropathy was reported in 33% of patients (grade 3–4 neuropathy in 3%) 64 . TDM‐1 also can cause peripheral neuropathy, occurred in 22% of patients (grade 3–4 neuropathy in 1.6%), and should be managed with dose delays until clinical improvement 65…”

Section: Systemic Treatmentmentioning

confidence: 99%

Neurologic complications of breast cancer

Atkins

Zimmer

2022

Cancer

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Breast cancer is a heterogeneous disease with unique neurologic complications that can arise from central nervous system (CNS) involvement or secondary to treatments themselves. As progress is made, with more targeted therapies and combinations available, particularly in the realm of human epidermal growth factor receptor 2 (HER2)-positive disease, the role of these new agents in patients with CNS disease is gradually evolving, although intracranial efficacy itself is lagging. At the same time, both systemic and local standard therapies pose clinical challenges regarding neurologic complications, such as peripheral neuropathy and cognitive changes. The development of new agents, such as immunotherapy, and new strategies, such as incorporating systemic therapies into local therapy, unveil new presentations of neurological complications.

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Section: Systemic Treatmentmentioning

confidence: 99%

Neurologic complications of breast cancer

Atkins

Zimmer

2022

Cancer

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“…In group of subjects treated with a-PD-1 or a-PDL-1 antibodies, the most common neurological adverse effect were headache, estimated for about 3% and myopathy/myalgia (3%). Grade 3 and 4 toxicity were very rare, with myasthenia gravis being the most common one, with the frequency of 1%, but example of grade 5 toxicity MG was noted (14) . In group of subjects treated with a-PD-1 antibodies, general estimated freqency of neurological irAEs was 2,9 (15) to 3,2% (14).…”

Section: Introductionmentioning

confidence: 99%

“…Grade 3 and 4 toxicity were very rare, with myasthenia gravis being the most common one, with the frequency of 1%, but example of grade 5 toxicity MG was noted (14) . In group of subjects treated with a-PD-1 antibodies, general estimated freqency of neurological irAEs was 2,9 (15) to 3,2% (14). Myositis seems to be the most frequent neuromuscular irAEs (16) .…”

Section: Introductionmentioning

confidence: 99%

Myasthenia gravis during treatment with anti-PD-1 - succesfull treatment using pirydostygminum – case report and literature review

Tywanek

Jankowska

Zwolak

et al. 2022

J Educ Health Sport

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Background: Against limited effectiveness of known oncological treatment such as chemio-and radiotherapy or surgery, new ways of treatment, such as for example immunotherapy has developed. Usage of immune checkpoint inhibitors (ICPIs), resulting in overactivation of immune system, may significantly raise efficacy of oncological treatment, but simultaneously predispose to occurrence various autoimmunological health complications. Adverse actions of the therapy may affect multiple organs and systems, with the presented example of immune-related neurological complication, myasthenia gravis. This relatively rare condition may be severe, life-threatening illness. Case report: We present a case of 66-year-old male patient diagnosted with a large tumor histopathologically assessed as squamous cell carcinoma. Due to ineffectiveness of implemented chemio- and radiotherapy, he was qualified for anti-PD1 immunotherapy with nivolumab. General treatment tolerance was very good with positive antineoplastic effect. Autoimmune hypothyroidism has emerged, therefore levothyroxine therapy has been implemented. After about a year of using immunotherapy, significant weakness and decrease in muscle strength has appeared, subsequently, immunotheraphy-related myasthenia gravis was raised. Improvement in the patient's condition was achieved after initiating pyridostigmine treatment. Cessation of antineoplastic treatment wasn’t necessary, what is unusual. Conclusions: Undeniably myastenia gravis may determine serious, life-threatening adverse effect of immunotherapy. Usually requires withdrawal of applied antioncological treatment, and should be treated with immunomodulators, immunosuppressants or intravenous immunoglobulins or plasmaphaeresis, however – as we present- in some cases may be properly cured only with pyridostygmine.

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“…Among these antibodies, the most commonly used in the treatment against HER2+ tumors are pertuzumab and trastuzumab, two recombinant humanized monoclonal antibodies [ 25 , 26 ]. Of these, trastuzumab (Herceptin TM , Genentech/Roche, San Francisco, FL, USA) (Tmab) specifically binds to the extracellular domain IV of the aforementioned HER2 and has allowed the survival rate of patients who suffer from HER2-positive (HER2+) breast cancer to increase [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

2020

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HER2 overexpression, which occurs in a fifth of diagnosed breast cancers as well as in other types of solid tumors, has been traditionally linked to greater aggressiveness. Nevertheless, the clinical introduction of trastuzumab has helped to improve HER2-positive patients’ outcomes. As a consequence, nanotechnology has taken advantage of the beneficial effects of the administration of this antibody and has employed it to develop HER2-targeting nanomedicines with promising therapeutic activity and limited toxicity. In this review, the molecular pathways that could be responsible for trastuzumab antitumor activity will be briefly summarized. In addition, since the conjugation strategies that are followed to develop targeting nanomedicines are essential to maintaining their efficacy and tolerability, the ones most employed to decorate drug-loaded nanoparticles and liposomes with trastuzumab will be discussed here. Thus, the advantages and disadvantages of performing this trastuzumab conjugation through adsorption or covalent bindings (through carbodiimide, maleimide, and click-chemistry) will be described, and several examples of targeting nanovehicles developed following these strategies will be commented on. Moreover, conjugation methods employed to synthesized trastuzumab-based antibody drug conjugates (ADCs), among which T-DM1 is well known, will be also examined. Finally, although trastuzumab-decorated nanoparticles and liposomes and trastuzumab-based ADCs have proven to have better selectivity and efficacy than loaded drugs, trastuzumab administration is sometimes related to side toxicities and the apparition of resistances. For this reason also, this review focuses at last on the important role that newer antibodies and peptides are acquiring these days in the development of HER2-targeting nanomedicines.

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Neurotoxicity of antibodies in cancer therapy: A review

Cited by 12 publications

References 34 publications

Neurologic complications of breast cancer

Neurologic complications of breast cancer

Myasthenia gravis during treatment with anti-PD-1 - succesfull treatment using pirydostygminum – case report and literature review

Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

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