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Investigational New Drugs
Erschienen in:

03.08.2023 | Research

Development and characterization of fused human arginase I for cancer therapy

verfasst von: Snehal Sainath Jawalekar, Priyanka Sugriv Kawathe, Nisha Sharma, J Anakha, Kulbhushan Tikoo, Abhay H. Pande

Erschienen in: Investigational New Drugs | Ausgabe 5/2023

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Abstract

Recombinant human arginase I (rhArg I) have emerged as a potential candidate for the treatment of varied pathophysiological conditions ranging from arginine-auxotrophic cancer, inflammatory conditions and microbial infection. However, rhArg I have a low circulatory half-life, leading to poor pharmacokinetic and pharmacodynamic properties, which necessitating the rapid development of modifications to circumvent these limitations. To address this, polyethylene glycol (PEG)ylated-rhArg I variants are being developed by pharmaceutical companies. However, because of the limitations associated with the clinical use of PEGylated proteins, there is a dire need in the art to develop rhArg I variant(s) which is safe (devoid of limitations of PEGylated counterpart) and possess increased circulatory half-life. In this study, we described the generation and characterization of a fused human arginase I variant (FHA-3) having improved circulatory half-life. FHA-3 protein was engineered by fusing rhArg I with a half-life extension partner (domain of human serum albumin) via a peptide linker and was produced using P. pastoris expression system. This purified biopharmaceutical (FHA-3) exhibits (i) increased arginine-hydrolyzing activity in buffer, (ii) cofactor - independency, (iii) increased circulatory half-life (t1/2) and (iv) potent anti-cancer activity against human cancer cell lines under in vitro and in vivo conditions.
Literatur
1.
Geiger R, Rieckmann JC, Wolf T, Basso C, Feng Y, Fuhrer T, Kogadeeva M, Picotti P, Meissner F, Mann M, Zamboni N (2016) L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell 167(3):829–842CrossRefPubMedPubMedCentral
2.
Anakha J, Kawathe PS, Datta S, Jawalekar SS, Banerjee UC, Pande AH (2022) Human arginase 1, a Jack of all trades? 3 Biotech 12(10):1–9CrossRef
3.
Feun L, You M, Wu CJ, Kuo MT, Wangpaichitr M, Spector S, Savaraj N (2008) Arginine deprivation as a targeted therapy for cancer. Curr Pharm Design 14(11):1049–1057CrossRef
4.
Delage B, Fennell DA, Nicholson L, McNeish I, Lemoine NR, Crook T, Szlosarek PW (2010) Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer. Int J Cancer 126(12):2762–2772PubMed
5.
Delage B, Luong P, Maharaj L, O’riain C, Syed N, Crook T, Hatzimichael E, Papoudou-Bai A, Mitchell TJ, Whittaker SJ, Cerio R (2012) Promoter methylation of argininosuccinate synthetase-1 sensitises lymphomas to arginine deiminase treatment, autophagy and caspase-dependent apoptosis. Cell Death Dis 3(7):e342–e342CrossRefPubMedPubMedCentral
6.
Jeon H, Kim JH, Lee E, Jang YJ, Son JE, Kwon JY, Lim TG, Kim S, Park JH, Kim JE, Lee KW (2016) Methionine deprivation suppresses triple-negative breast cancer metastasis in vitro and in vivo. Oncotarget 7(41):67223-67234CrossRefPubMedPubMedCentral
7.
8.
Stone EM, Glazer ES, Chantranupong L, Cherukuri P, Breece RM, Tierney DL, Curley SA, Iverson BL, Georgiou G (2010) Replacing Mn2+ with Co2+ in human arginase I enhances cytotoxicity toward L-arginine auxotrophic cancer cell lines. ACS Chem Biol 5(3):333–342CrossRefPubMedPubMedCentral
9.
Cheng PN, Lam TL, Lam WM, Tsui SM, Cheng AW, Lo WH, Leung YC (2007) Pegylated recombinant human arginase (rhArg-peg5, 000mw) inhibits the in vitro and in vivo proliferation of human hepatocellular carcinoma through arginine depletion. Cancer Res 67(1):309–317CrossRefPubMed
10.
Lam TL, Wong GK, Chow HY, Chong HC, Chow TL, Kwok SY, Cheng PN, Wheatley DN, Lo WH, Leung YC (2011) Recombinant human arginase inhibits the in vitro and in vivo proliferation of human melanoma by inducing cell cycle arrest and apoptosis. Pigment cell melanoma res 24(2):366–376CrossRefPubMed
11.
Patil MD, Bhaumik J, Babykutty S, Banerjee UC, Fukumura D (2016) Arginine dependence of tumor cells: targeting a chink in cancer’s armor. Oncogene 35(38):4957–4972CrossRefPubMedPubMedCentral
12.
Glazer ES, Stone EM, Zhu C, Massey KL, Hamir AN, Curley SA (2011) Bioengineered human arginase I with enhanced activity and stability controls hepatocellular and pancreatic carcinoma xenografts. Translational Oncol 4(3):138–146CrossRef
13.
Chung SF, Kim CF, Tam SY, Choi MC, So PK, Wong KY, Leung YC, Lo WH (2020) A bioengineered arginine-depleting enzyme as a long-lasting therapeutic agent against cancer. Appl Microbiol Biotechnol 104(9):3921–3934CrossRefPubMed
14.
Langenheim JF, Chen WY (2009) Improving the pharmacokinetics/pharmacodynamics of prolactin, GH, and their antagonists by fusion to a synthetic albumin-binding peptide. J Endocrinol 203(3):375CrossRefPubMed
15.
Fee CJ, Van Alstine JM (2011) Purification of pegylated proteins.  Methods Biochem Anal 54, 339–362CrossRef
16.
Li L, Wang Y, Chen J, Cheng B, Hu J, Zhou Y, Gao X, Gao L, Mei X, Sun M, Zhang Z (2013) An engineered arginase FC protein inhibits tumor growth in vitro and in vivo. Evid Based Complement Alternat Med eCAM, 423129
17.
Haeckel A, Appler F, Ariza de Schellenberger A, Schellenberger E (2016) XTEN as Biological Alternative to PEGylation allows complete expression of a protease-activatable killin-based cytostatic. PLoS ONE 11(6):e0157193CrossRefPubMedPubMedCentral
18.
Iyengar AS, Gupta S, Jawalekar S, Pande AH (2019) Protein chimerization: a new frontier for engineering protein therapeutics with improved pharmacokinetics. J Pharmacol Exp Ther 370(3):703–714CrossRefPubMed
19.
Kontermann RE (2011) Strategies for extended serum half-life of protein therapeutics. Curr Opin Biotechnol 22(6):868–876CrossRefPubMed
20.
Zaman R, Islam RA, Ibnat N, Othman I, Zaini A, Lee CY, Chowdhury EH (2019) Current strategies in extending half-lives of therapeutic proteins. J Control Release 301:176–189CrossRefPubMed
21.
22.
Sockolosky JT, Tiffany MR, Szoka FC (2012) Engineering neonatal fc receptor-mediated recycling and transcytosis in recombinant proteins by short terminal peptide extensions. Proc Natl Acad Sci 109(40):16095–16100CrossRefPubMedPubMedCentral
23.
Dennis MS, Zhang M, Meng YG, Kadkhodayan M, Kirchhofer D, Combs D, Damico LA (2002) Albumin binding as a general strategy for improving the pharmacokinetics of proteins. J Biol Chem 277(38):35035–35043CrossRefPubMed
24.
Chen X, Zaro J, Shen WC (2013) Fusion protein linkers: effects on production, bioactivity, and pharmacokinetics. Fusion protein technologies for biopharmaceuticals: applications and challenges, 57–73
25.
Bajaj P, Tripathy RK, Aggarwal G, Datusalia AK, Sharma SS, Pande AH (2016) Refolded recombinant human paraoxonase 1 variant exhibits prophylactic activity against organophosphate poisoning. Appl Biochem Biotechnol 180(1):165–176CrossRefPubMed
26.
Schabbauer G, Bluml S, Sahin-Heco E, Cheng P, Chen L (2017) Methods and compositions for modulating the immune system with arginase I. (U.S. Patent No. 9789169B2)
27.
Kaur J, Tikoo K (2015) Ets1 identified as a novel molecular target of RNA aptamer selected against metastatic cells for targeted delivery of nano-formulation. Oncogene 34(41):5216–5228CrossRefPubMedPubMedCentral
28.
Surapaneni SK, Bhat ZR, Tikoo K (2020) MicroRNA-941 regulates the proliferation of breast cancer cells by altering histone H3 ser 10 phosphorylation. Sci Rep 10(1):1–17CrossRef
29.
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63CrossRefPubMed
30.
Karbalaei M, Rezaee SA, Farsiani H (2020) Pichia pastoris: a highly successful expression system for optimal synthesis of heterologous proteins. J Cell Physiol 235(9):5867–5881CrossRefPubMedPubMedCentral
31.
Macauley-Patrick S, Fazenda ML, McNeil B, Harvey LM (2005) Heterologous protein production using the Pichia pastoris expression system. Yeast 22(4):249–270CrossRefPubMed
32.
Ikemoto M, Tabata M, Miyake T, Kono T, Mori M, Totani M, Murachi T (1990) Expression of human liver arginase in Escherichia coli. Purification and properties of the product. Biochem J 270(3):697–703CrossRefPubMedPubMedCentral
33.
Cheng NM (2012) Use of pegylated recombinant human arginase for treatment of leukemia. (U.S. Patent No. 20130295073A1).
34.
Cheng NM, Chen L (2015) Human arginase and pegylated human arginase and the use thereof. (U.S. Patent No. 9109218B2).
35.
Leung YC, Shum SW (2019) Composition and application of arginine-depleting agents for cancer, obesity, metabolic disorders, and related complications and comorbidities. (International publication No. WO 2019/ 228510 A1).
36.
Cheng NM (2008) Pharmaceutical Composition and Method of treating Hepatitis with Arginases. (U.S. Patent No. 20080299638A1)
37.
Hsueh EC, Knebel SM, Lo WH, Leung YC, Cheng PN, Hsueh CT (2012) Deprivation of arginine by recombinant human arginase in prostate cancer cells. J Hematol Oncol 5(1):1–6CrossRef
38.
Chung SF, Kim CF, Kwok SY, Tam SY, Chen YW, Chong HC, Leung SL, So PK, Wong KY, Leung YC, Lo WH (2020) Mono-PEGylation of a thermostable arginine-depleting enzyme for the treatment of lung cancer. Int J Mol Sci 21(12):4234CrossRefPubMedPubMedCentral
39.
Zhang Y, Chung SF, Tam SY, Leung YC, Guan X (2021) Arginine deprivation as a strategy for cancer therapy: an insight into drug design and drug combination. Cancer Lett 502:58–70CrossRefPubMed
40.
Kontermann RE (2016) Half-life extended biotherapeutics. Expert Opin Biol Ther 16(7):903–915CrossRefPubMed
41.
42.
43.
Fang L, Jiang Y, Yang Y, Zheng Y, Zheng J, Jiang H, Zhang S, Lin L, Zheng J, Zhang S, Zhuang X (2016) Determining the optimal 5-FU therapeutic dosage in the treatment of colorectal cancer patients. Oncotarget 7(49):81880CrossRefPubMedPubMedCentral
Metadaten
Titel
Development and characterization of fused human arginase I for cancer therapy
verfasst von
Snehal Sainath Jawalekar
Priyanka Sugriv Kawathe
Nisha Sharma
J Anakha
Kulbhushan Tikoo
Abhay H. Pande
Publikationsdatum
03.08.2023
Verlag
Springer US
Erschienen in
Investigational New Drugs / Ausgabe 5/2023
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-023-01387-y

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