- Medicinal Chemistry | Clinical Chemistry | Forensic Chemistry | Natural Chemistry | Electrochemistry | Geochemistry | Oncolytic Virotherapy | Immunopharmacotherapy | Analytical Biotherapeutics
Location: Dallas
Chair
Montasser Altorgoman
Alexandria University, Egypt
Session Introduction
Jianyong Wang
Genentech, USA
Title: Combining immunoassay and LC/MS to characterize stability of antibody therapeutics In Vivo
Biography:
Jerry Wang received his PhD from the Deaprtment of Biochemistry and Molecular Biology at Medical Univisity of Ohio (Toledo, OH). After Post-doctoral studies at Univsersity of Michigan Medical Center, he began his industry career as a Pharmcologist. He is currently a Scientist in the Department of Biochemical and Cellular Pharmacology at Genentech. His group supports the therapeutic antibody programs during research and early development phases. His main responsibilities include antibody screening and characterization by in vitro and in vivo studies to select clinical candidates. He has worked in biopharmaceutical industry for more than 15 years including 10 years at Genentech for biotherapeutics R&D.
Abstract:
As many of therapeutic biologics (including monoclonal antibodies and antibody-drug conjugates) enter the frontline of disease treatment, tracking their stability in vivo, is a critical step in development of these therapeutics. Unstable antibody therapeutics (including unstable antibody-drug conjugates) may cause decreased drug activity, fast clearance, increased immunogenicity, and safety issues (toxicities). Non enzyme-mediated deamidation is a common protein degradation that normally occurs on asparagine (and to a lesser extent, glutamine residues), resulting in a conversion to aspartic and isoaspartic
acids with a mass shift of +0.984 Da. To monitor the deamidation of therapeutic antibodies dosed in vivo, we developed analytical methods with the combination of immunoassay and LC/MS using peptide level MS detection. We further optimized the process and established an automated high throughput method allowing for high fi delity deamidation analysis of human
antibodies from in vivo study samples. Similarly, we were also able to characterize the stability of antibody-drug conjugates in vivo, by using the combination of affi nity-capture and intact protein MS analysis. Th ese procedures will help to exclude unstable drug candidates at early development phase, and select stable antibody-based therapeutics for clinical applications.
Biography:
Montasser Altorgoman, is currently a PhD candidate at the Alexandria University, Egypt Faculty of Science, Department of biochemistry. In addition he is as a biochemist at the Toxins lab at the Ministry of health. Since the usage of Interferon for treatment of Virus C patients specially genotype 4 is inevitable, so the question is could be the side effects of the Interferon prohibited and the contraindications to the Interferon treatment might be evaded. Hence his all focus is for fi nding new techniques like liposomal delivery and/or a new adjuvant therapy specially the natural ones to ameliorate side effects of the treatment.
Abstract:
Liver fi brosis is the wound healing response to a variety of acute or chronic stimuli, for instance viral infection, toxins and metabolic diseases. Th e pattern of hepatic stellate cell activation provides an important framework to pinpoint
sites of antifi brotic therapy. IFN exhibit a wide spectrum of biological activities in target cells including antiviral, immunomodulatory, anti angiogenic and growth-inhibitory eff ects. Th e antiproliferative eff ects of IFN are the rational basis for their use in the treatment of metastatic malignant melanoma and renal cell carcinoma. Th e food use of S. oleraceus is justifi ed
by the high content of vit. C, fl avonoids and phenolics. Th e previous studies discussed the antifi brotic eff ect of IFN and S. oleraceus individually on liver fi brosis but in this study the combination treatment has been studied well in the induced liver fi brosis models. Using diff erent immunoassays, histopathol-ogy, colorimetric and PCR techniques results obtained showed that TAA causes hepatic fi brosis by induction of free radical production and decrease cellular antioxidant stores. Th e different treatment ways including combination treatment group showed a signifi cant inhibi-tory eff ect in targeting hepatic fi brosis by reducing oxidative stress, increasing the activity of antioxidant enzymes and by inhibiting HSCs infl ammation, activation
and proliferation through increasing the levels of antifi brotic co-transcription factor PPAR-γ and decrease the levels of the main HSCs fi brogenic cytokines TGFβ1 and PDGF-BB. In conclusion, bio-chemical, molecular and histopathological fi ndings demonstrated that the combination treatment improved the antifi brotic eff ect better than the individual one, the prophylactic usage of SE protected against hepatic fi brosis and SE had no side eff ect.
- Polymer Chemistry | Quantum Chemistry | Innovative Therapies for Serious Diseases | Chromatographic Techniques | Cancer Biotherapeutics | Advancements in Biotherapeutics
Location: Dallas
Session Introduction
Annette Frenk Oquendo
University of Houston, USA
Title: Transcriptome analysis of colchicine producing plant species: Gloriosa superba and Colchicum autumnale
Biography:
Abstract:
Colchicine is a FDA-approved plant-based alkaloid that is commonly used to treat gout. It has also been proven to bebeneficial in cardiovascular diseases and its antimitotic properties make it a promising cancer treatment. Traditionally, the natural isomer of colchicine is extracted from Gloriosa superba, which was initially isolated from Colchicum autumnale. The biosynthetic pathway of colchicine is not yet characterized, and the pathway genes and mechanisms must be elucidated to improve colchicine production. G. superba and C. autumnale transcriptomes were analyzed and compared against NCBI and Swissprot protein databases to identify the biosynthetic pathway genes. Th e annotation data of these transcriptomes revealed that there were 60927 assembled multi-tissue transcripts of C. autumnale, which represented 21945 unigenes. Additionally, G.superba has 32312 assembled multi-tissue transcripts which represented 15088 unigenes in known plant-specifi c Gene Ontology (GO). Gene annotation and pathway mapping data will be presented.
Santhana Krishnan
University of Houston, USA
Title: Computational fluid mechanics in biomanufacturing
Biography:
Abstract:
Gloriosa superba is a commercial source of the pharmaceutical colchicine. Colchicine is one of the primary sources of
treatment for gout. Th e balloon type bubble reactor (BTBR) has been successfully used to biomanufacture bioactive small
molecules. Colchicine production can be improved by understanding the fl uid mechanics inside this reactor, which primarily
depends on several parameters such as reactor working volumes, diameter of the sparger, fl ow rate, viscosity, surface tension,
density of the fl uids, and nutrient volume fractions. Our initial bioimaging study suggests that in 4L BTBR at low air injection
rate the fl ow ascends up a fairly straight vertical path, concentrating mostly toward the center of the reactor. However, at
higher injection rates, a more chaotic fl ow forms. Th e post processed images reveal that the fl ow patterns inside the reactor
vary, as positive and negative vorticity zones. We will present the clockwise/counter-clockwise directions of the dimensionless
mapping of fl uid dynamics data. Th is analysis will not only address the geometric patterns of mixing, but will also apply to the
nature of liquids, solutions, and injection gases with various combinations of density, viscosity, and surface tension that will
eventually improve the colchicine biomanufacturing design process.
John Samuel Bass
University of Houston, USA
Title: Identification of genes related to the development of Gloriosa superba rhizome
Biography:
Abstract:
The pharmaceutical demand for plant-based colchicine is increasing because it is an eff ective FDA-approved gout medicine that also has potential for cancer therapeutics due to its ability to bind to microtubules and halt cell division. Understanding the biorhizome developmental genes are necessary to improve the biomanufacturing of colchicine. RNA-Seq was used to identify the rhizome developmental genes from Gloriosa superba and Colchicum autumnale. Th e transcriptome of both species were compared against NCBI and Swissprot protein databases. Python scripts were utilized to parse the transcriptome.
Bioinformatics analysis revealed 60927 assembled multiple-tissue transcripts of C. autumnale represented 21948 unigenes and G. superba has 32312, which represented 15089 unigenes in known plant specifi c gene ontology (GO). Further GO analysis was used to identify known rhizome-specifi c and developmental genes in G. superba. Th is study could provide a foundation to
enhance the biorhizome-based colchicine biomanufacturing in G. superba.
Banda J M
Kaduna State University, Nigeria
Title: Maternal serum cytokines and pregnancy specific beta-1 glycoprotein in normal pregnancies and those complicated by eclampsia in Kaduna state
Biography:
Banda J M has his expertise in Medical Laboratory Science with PhD in Immunology. He believes that quality laboratory results is achievable and can be a veritable tool in improving health and wellbeing of Nigerians. He leads a team (quality team) of Medical Laboratory Scientists and together they have been able to achieve an in-country CDC/Afro Accreditation through the Strengthening of Laboratory Management toward Accreditation (SLMTA) curriculum and WHO Stepwise Laboratory Improvement Process towards Accreditation (SLIPTA) checklist. He has achieved this after years of experience in research, teaching and administration both in hospital and education institutions. He has developed special interest in Maternal Health and believes that through research the high maternal morbidity and mortality rate in Nigeria could be reduced to the barest minimum, especially in the Northern part of Nigeria where there is high level of poverty and poor healthseeking behavior.
Abstract:
Statement of Problem: Eclampsia (EC) is the life-threatening occurrence of convulsion(s) in association with hypertension and proteinuria in human pregnancy. It has remained a signifi cant public health threat, contributing to signifi cant maternal and perinatal morbidity and mortality in Nigeria, though the mechanism of the disease is not fully understood and there is no cure, it is widely held that an immunological mechanism is involved. Disturbance of the cytokines equilibrium has been accused for many pathological disorders including EC.
Subject & Method: Enzyme linked immunoassay (ELSA) was used to measure levels of pro-infl ammatory cytokines (TNF-α, IL -2), anti-infl ammatory cytokines (IL-4, IL-10) and PSG-1 in the peripheral blood of patients with eclampsia (EC; n=38), normal healthy pregnant women (PC; n=25) and compared with healthy non pregnant controls (NPC; n=25).
Findings: Th e overall result of TNF-α (2.34 ±0.13 pg/ml) in EC was signifi cantly higher than the mean values (2.25±0.07 pg/ ml and 2.24±0.10 pg/ml) in PC and NPC respectively. Furthermore, EC had higher TNF-α mean value compared with NPC (P<0.05). Th ere was no statistical diff erence in mean IL-2 value between EC (1.69±0.17 pg/ml), PC (1.71±0.0.09 pg/ml) and NPC (1.72±0.13 pg/ml) (P>0.05). Th e mean value of IL-10 was lower in EC (1.28±0.54 pg/ml) compared with PC (1.58±0.61 pg/ml) and NPC (2.06±0.08 pg/ml). No signifi cant diff erence in IL-4 mean value exist between EC (2.45±0.10 pg/ml) and NPC (2.45 pg/ml) (P>0.05) but signifi cant diff erence exist between EC and NPC (2.40±0.06 pg/ml) (P<0.05). Th e serum PSG-1 levels in EC (2.53±0.11 pg/ml) and PC (2.56±0.03 pg/ml) were similar and signifi cantly higher than in NPC (0.06±0.020 pg/ml) P<0.05.
Conclusion: While a pro-infl ammatory cytokine environment was demonstrated in EC, and decreased anti-infl ammatory reactivity, EC was not as associated with low levels of PSG-1. Further research is advocated to discover how anti-infl ammatory cytokines could be exploited as a therapeutic agent for women at high risk of eclampsia.