scholarly journals Mono-PEGylation of a Thermostable Arginine-Depleting Enzyme for the Treatment of Lung Cancer

2020 ◽  
Vol 21 (12) ◽  
pp. 4234 ◽  
Author(s):  
Sai-Fung Chung ◽  
Chi-Fai Kim ◽  
Sui-Yi Kwok ◽  
Suet-Ying Tam ◽  
Yu Wai Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Safety Issue ◽  
Xenograft Model ◽  
Fold Increase ◽  
Arginine Deiminase ◽  
Phase Iii ◽  
Cancer Cell Growth ◽  
Phase Iii Clinical Trials ◽  
Elimination Half ◽  
Lung Cancer Therapy

L-arginine (L-Arg) depletion induced by randomly PEGylated arginine deiminase (ADI-PEG20) can treat arginosuccinate synthase (ASS)-negative cancers, and ADI-PEG20 is undergoing phase III clinical trials. Unfortunately, ASS-positive cancers are resistant to ADI-PEG20. Moreover, the yield of ADI production is low because of the formation of inclusion bodies. Here, we report a thermostable arginine-depleting enzyme, Bacillus caldovelox arginase mutant (BCA-M: Ser161->Cys161). An abundant amount of BCA-M was easily obtained via high cell-density fermentation and heat treatment purification. Subsequently, we prepared BCA-M-PEG20, by conjugating a single 20 kDa PEG monomer onto the Cys161 residue via thio-chemistry. Unlike ADI-PEG20, BCA-M-PEG20 significantly inhibited ASS-positive lung cancer cell growth. Pharmacodynamic studies showed that a single intraperitoneal injection (i.p). administration of 250 U/mouse of BCA-M-PEG20 induced low L-Arg level over 168 h. The mono-PEGylation of BCA-M prolonged its elimination half-life from 6.4 to 91.4 h (a 14-fold increase). In an A549 lung cancer xenograft model, a weekly administration of 250 U/mouse of BCA-M-PEG20 suppressed tumor growth significantly. We also observed that BCA-M-PEG20 did not cause any significant safety issue in mouse models. Overall, BCA-M-PEG20 showed excellent results in drug production, potency, and stability. Thereby, it has great potential to become a promising candidate for lung cancer therapy.

scholarly journals Small Interfering RNA (siRNA) of Mini circle DNA Transfection (McD) is Encapsulated by Gold Nanoparticles from Folate’s Receptors of Gold Conjugation as Curative Therapy for Non-Small’s Cell of Lung Cancer

2021 ◽  
Vol 6 (2) ◽  
pp. 237-246
Author(s):  
Agung Wiwiek Indrayani ◽  
I Gusti Ayu Sitti Sadvika ◽  
I Gede Wikania Wira Wiguna ◽  
Ni Putu Sri Indrani Remitha ◽  
I Gede Krisna Arim Sadeva ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Target Therapy ◽  
Gene Transfection ◽  
Relevant Literature ◽  
Phase Iii ◽  
Curative Therapy ◽  
Phase Iii Clinical Trials ◽  
Therapeutic Opportunity ◽  
The Right ◽  
Interfering Rna

Background: Lung cancer is one of the non-communicable diseases that have an increasing number of events that each year with a mortality rate of 18.4% and an incidence of 11.6%, occupies the top position based on GLOBOCAN data in 2018. One of management in the NSCLC is currently in the form of surgery and adjuvant therapy such as chemotherapy, radiotherapy and target therapy. However, there were weaknesses and limitations in care for its patients therefore development of curative therapy for NSCLC’s patients were needed.  The aim of this review is to learn and investigate about the potential of siRNA that is transfected into McD and folate receptors alpha-conjugated gold nanoparticle encapsulation as a therapeutic opportunity that could be developed as a treatment in management of NSCLC.Method: The writing method used in this review article was the study method of literature.  The used data comes from 45 of relevant literature sources and was arranged systematically in accordance with the topic of the problem discussed, along with the inclusion and exclusion criteria.Result: This treatment could increase gene transfection, siRNA biodistribution in organs, reduced KRAS, Bcl-2, and VEGF expression.  Moreover, siRNA had entered phase III clinical trials and FOLR1 antibodies were in phase II of clinical trials.Conclusion: Utilization of siRNA specifically was designed for three genes such for KRAS, VEGF and Bcl-2 which were three genes that played a role in the pathogenesis of NSCLC, could be the right modality choice for treatment of NSCLC. 

scholarly journals Clinical Efficacy and Future Prospects of Immunotherapy in Lung Cancer

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1029
Author(s):  
Tomonari Kinoshita ◽  
Hideki Terai ◽  
Tomonori Yaguchi
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Phase Iii ◽  
Future Prospects ◽  
Phase Iii Clinical Trials ◽  
Current Therapies ◽  
New Treatment ◽  
Related Mortality

The three major conventional treatments: surgery, chemotherapy, and radiation therapy, have been commonly performed for lung cancer. However, lung cancer is still the leading cause of cancer-related mortality. Immunotherapy has recently emerged as a very effective new treatment modality, and there is now growing enthusiasm for cancer immunotherapy worldwide. However, the results of clinical studies using immunotherapy are not always favorable. Understanding the steps involved in the recognition and eradication of cancer cells by the immune system seems essential to understanding why past immunotherapies have failed and how current therapies can be optimally utilized. In addition, the combination of immunotherapies, such as cancer vaccines and immune checkpoint inhibitors, as well as the combination of these therapies with three conventional therapies, may pave the way for personalized immunotherapy. In this review, we summarize the results of immunotherapies used in phase III clinical trials, including immune checkpoint inhibitors, and discuss the future prospects of immunotherapies in lung cancer treatment.

scholarly journals In silico and in vitro analysis of recombinant arginine deiminase from Pseudomonas furukawaii as a potential anticancer enzyme

2021 ◽  
Author(s):  
Rakhi Dhankhar ◽  
Vatika Gupta ◽  
Aparajita Mohanty ◽  
Pooja Gulati
Keyword(s):  
In Silico ◽  
3D Structure ◽  
Cell Epitope ◽  
Mycoplasma Hominis ◽  
Arginine Deiminase ◽  
Phase Iii ◽  
Drug Candidate ◽  
Phase Iii Clinical Trials ◽  
Vitro Analysis

Abstract Arginine deiminase (ADI) is a promising anticancer enzyme that can be employed in amino acid deprivation therapy for the treatment of various arginine auxotrophic tumors. In our previous work, Pseudomonas furukawaii was identified as a potent producer of ADI with optimum activity at physiological pH and temperature. The 3D structure of PfADI was modeled. Immunoinformatics analysis was also carried out to compare the immunogenicity of PfADI with MhADI (Mycoplasma hominis ADI, which is in phase III clinical trials). The PfADI was found to be less immunogenic in terms of number of linear and conformational B cell epitopes and T cell epitope density. The overall antigenicity and allergenicity of PfADI was also lower as compared to MhADI. Thus, the ADI coding arcA gene was cloned and expressed in E. coli BL21. Recombinant ADI of P. furukawaii (PfADI) was purified using affinity chromatography and its molecular mass was estimated to be ~46KDa. PfADI was found to effectively inhibit the HepG2 cells with an IC50 value of 0.1950 IU/ml. PfADI was characterized and the enzyme was found to be stable at human physiological conditions (pH 7 and 37 ⁰C temperature). The Km and Vmax values were found to be 1.90 mM and 1.83 µmol ml-1min-1 respectively. Thus the present in vitro and in silico studies establish PfADI as a potential anticancer drug candidate with improved efficacy and low immunogenicity.

Rome I versus Rome II; Overlap in patients enrolled in tegaserod phase III clinical trials for irritable bowel syndrome (IBS)

2001 ◽  
Vol 120 (5) ◽  
pp. A284-A284
Author(s):  
B NAULT ◽  
S SUE ◽  
J HEGGLAND ◽  
S GOHARI ◽  
G LIGOZIO ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Irritable Bowel Syndrome ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Irritable Bowel ◽  
Rome I
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