Evaluation of PEG-L-asparaginase in asparagine suppression and anti-drug antibody development in healthy Beagle dogs: A multi-phase preclinical study

Feenstra, Laurien; Gehring, Ronette; Geijswijk, I M van; König, Thorsten; Prinsen, Hubertus C.M.T.; Vandemeulebroecke, Katrien; Lammens, Tim; Krupa, Adriana; Teske, Erik

doi:10.1016/j.tvjl.2022.105854

Cited by 5 publications

(4 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7,10,12,16 The short duration of responses could be related to the development of anti-asparaginase antibodies, neutralising the asparaginase and resulting in rebounding of amino acids in serum, as seen in people, and recently confirmed in dogs. 28,31 To date, this has not been confirmed in cats.…”

Section: Discussionmentioning

confidence: 93%

“…26 In canine lymphoma, PEGasp was reported to be as effective as l-asparaginase without significant AEs. 27,28 A recent study confirmed the effectiveness of PEGasp in addition to a modified cyclophosphamide, vincristine and prednisolone (COP) regime in feline patients. 29 The objective of this study was to investigate the efficacy of PEGasp monotherapy for feline intermediate and large cell lymphoma of different anatomic locations as a potential alternative to palliative corticosteroids treatment in animals whose owners declined cytotoxic chemotherapy.…”

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Pegylated-l-asparaginase therapy for feline large cell lymphoma: 82 cases (2017–2020)

Bik,

Ruijter,

Van den Bossche

et al. 2023

Journal of Feline Medicine and Surgery

View full text Add to dashboard Cite

Objectives The present study aimed to investigate pegylated-l-asparaginase monotherapy for feline large cell lymphoma as a potential alternative to palliative corticosteroids treatment in animals whose owners declined cytotoxic chemotherapy. Methods A retrospective, descriptive case series of cats treated initially with pegylated-l-asparaginase as a sole therapy for feline large cell lymphoma is reported. The treatment protocol consisted of 12 intramuscular injections of pegylated-l-asparaginase with increasing intervals. If cats were unresponsive to pegylated-l-asparaginase monotherapy, a second-line treatment was initiated. Signalment, origin of lymphoma, staging, treatment, possible adverse events and follow-up data were extracted from the medical records. Responses and survival data were analysed. Results Eighty-two cats with lymphoma of five different anatomic types were included: alimentary, abdominal extra-alimentary, peripheral nodal, nasal/nasopharyngeal and other (mediastinal, renal [solitary] and miscellaneous combined in one group for analytical purposes). The response rate was 74.1% (95% confidence interval = 63.4–83.5) with 38.3% (95% confidence interval = 27.8–48.8) in complete remission. The median disease-free period and calculated overall survival time were 70 days (12–1702+) and 79 days (1–1715+), respectively. The response rate was significantly correlated with the origin of the lymphoma and the combined group had a significantly lower response rate ( P = 0.035). Twenty-four cats were also treated with corticosteroids. There was no significant difference in outcomes between the group treated with or without corticosteroids. Adverse events were present in a small number of cats (14/82). The majority of these adverse events were mild to moderate in 5/14 cats; however, the adverse events were severe enough to cause discontinuation of therapy. Conclusions and relevance Based on the response rate and median disease-free period, treatment with pegylated-l-asparaginase is inferior when compared with historical chemotherapy protocols. However, some cats demonstrated an exceptional long disease-free period. Therefore, pegylated-l-asparaginase could be offered as an alternative to corticosteroid therapy alone. Further studies are needed to evaluate the additional benefit over palliative corticosteroid monotherapy.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

Pegylated-l-asparaginase therapy for feline large cell lymphoma: 82 cases (2017–2020)

Bik,

Ruijter,

Van den Bossche

et al. 2023

Journal of Feline Medicine and Surgery

View full text Add to dashboard Cite

show abstract

“…These problems arise in part from their microbiological origin and strong immunological response [9]. To minimize adverse effects, several alternatives have been explored, including L-asparaginase from different sources, protein engineering and enzyme immobilization [10].…”

Section: Introductionmentioning

confidence: 99%

Production, Characterization, Purification and Antitumor Activity of L-asparaginase from <em>Aspergillus niger</em>

da Silva Duarte,

de Carvalho Silva,

Assunção Borges

et al. 2024

Preprint

View full text Add to dashboard Cite

Cervical cancer is caused by a persistent and high-grade infection, caused by the Human Papilloma Virus (HPV), which, when entering cervical cells, alters their physiology and generates serious lesions. HPV 18 - is among those most involved in carcinogenesis in this region, but there are still no drug treatments that cause cure or total remission of lesions caused by HPV. Knowing that L-Asparaginase is an amidohydrolase, which plays a significant role in the pharmaceutical industry, particularly in the treatment of specific cancers, due to its antitumor properties, some studies have demonstrated its cytotoxic effect against cervical cancer cells. However, the commercial version of this enzyme has side effects, such as hypersensitivity, allergic reactions and silent inactivation due to the formation of antibodies. To mitigate these adverse effects, several alternatives have been explored, including the use of L-asparaginase from other microbiological sources, which is the case with the use of the fungus Aspergillus niger, a high producer of L-asparaginase. The study investigated the influence of the type of fermentation, precipitant, purification, characterization and in vitro cytotoxicity of L-asparaginase. The results revealed that semisolid fermentation produced higher enzymatic activity and protein concentration of A. niger. The characterized enzyme showed excellent stability at pH 9.0, temperature of 50ºC, resistance to surfactants and metallic ions, and an increase in enzymatic activity was also noted with the organic solvent ethanol. Furthermore, it exhibited low cytotoxicity in GM and RAW cells, and significant cytotoxicity in HeLa cells. These findings indicate that L-asparaginase derived from Aspergillus niger may be a promising alternative for pharmaceutical production. Its attributes, including stability, activity and low toxicity in healthy cells, suggest that this modified enzyme could overcome challenges associated with antitumor therapy.

show abstract

Impact of concerning excipients on animal safety: insights for veterinary pharmacotherapy and regulatory considerations

Thomazini,

da Cunha,

Guimarães

et al. 2023

DARU J Pharm Sci

View full text Add to dashboard Cite

Evaluation of PEG-L-asparaginase in asparagine suppression and anti-drug antibody development in healthy Beagle dogs: A multi-phase preclinical study

Cited by 5 publications

References 28 publications

Pegylated-l-asparaginase therapy for feline large cell lymphoma: 82 cases (2017–2020)

Pegylated-l-asparaginase therapy for feline large cell lymphoma: 82 cases (2017–2020)

Production, Characterization, Purification and Antitumor Activity of L-asparaginase from <em>Aspergillus niger</em>

Impact of concerning excipients on animal safety: insights for veterinary pharmacotherapy and regulatory considerations

Contact Info

Product

Resources

About