Biologics

13 pages, 670 KiB

Open AccessReview

Targeting Hyaluronan Synthesis in Cancer: A Road Less Travelled

by Theodoros Karalis

Biologics 2023, 3(4), 402-414; https://doi.org/10.3390/biologics3040022 - 12 Dec 2023

Viewed by 2487

Hyaluronan is one of the major components of the extracellular matrix and is involved in the regulation of multiple processes in both human physiology and disease. In human cancers, hyaluronan metabolism displays remarkable alterations, leading to the accumulation of large amounts of hyaluronan [...] Read more.

Hyaluronan is one of the major components of the extracellular matrix and is involved in the regulation of multiple processes in both human physiology and disease. In human cancers, hyaluronan metabolism displays remarkable alterations, leading to the accumulation of large amounts of hyaluronan matrices in the tumoural tissues. The altered levels of hyaluronan in the tumours stem from the enhanced expression and activity of hyaluronan synthases in both tumour and stromal cells. Moreover, hyaluronidase activity is also upregulated in cancer, leading to the generation of lower molecular weight hyaluronan fragments that in turn assist tumour growth, neo-angiogenesis and the metastatic cascade. Hyaluronan accumulation in malignant tissues not only assists tumour growth and metastases but is also associated with worse outcomes in cancer patients. Therefore, targeting hyaluronan synthesis emerges as an interesting strategy that might be employed for cancer treatment. This review article summarises current evidence and discusses ways to move forward in the field of targeting hyaluronan synthesis for cancer therapy. Full article

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22 pages, 1253 KiB

Open AccessReview

Advances in Escherichia coli-Based Therapeutic Protein Expression: Mammalian Conversion, Continuous Manufacturing, and Cell-Free Production

by Sarfaraz K. Niazi and Matthias Magoola

Biologics 2023, 3(4), 380-401; https://doi.org/10.3390/biologics3040021 - 29 Nov 2023

Cited by 11 | Viewed by 9106

Abstract

Therapeutic proteins treat many acute and chronic diseases that were until recently considered untreatable. However, their high development cost keeps them out of reach of most patients around the world. One plausible solution to lower-cost manufacturing is to adopt newer technologies like using [...] Read more.

Therapeutic proteins treat many acute and chronic diseases that were until recently considered untreatable. However, their high development cost keeps them out of reach of most patients around the world. One plausible solution to lower-cost manufacturing is to adopt newer technologies like using Escherichia coli to express larger molecules, including full-length antibodies, generally relegated to Chinese Hamster Ovary (CHO) cells, adopt continuous manufacturing, and convert the manufacturing to cell-free synthesis. The advantages of using E. coli include a shorter production cycle, little risk of viral contamination, cell host stability, and a highly reproducible post-translational modification. Full article

(This article belongs to the Section Protein Therapeutics)

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25 pages, 3655 KiB

Open AccessReview

mRNA and Synthesis-Based Therapeutic Proteins: A Non-Recombinant Affordable Option

by Sarfaraz K. Niazi and Matthias Magoola

Biologics 2023, 3(4), 355-379; https://doi.org/10.3390/biologics3040020 - 15 Nov 2023

Cited by 4 | Viewed by 4145

Abstract

Recombinant technology has been around for nearly three quarters of a century and has revolutionized protein therapy. However, the cost of developing recombinant therapeutic proteins and the manufacturing infrastructure keeps their cost unaffordable for most patients. Proteins are produced in the body via [...] Read more.

Recombinant technology has been around for nearly three quarters of a century and has revolutionized protein therapy. However, the cost of developing recombinant therapeutic proteins and the manufacturing infrastructure keeps their cost unaffordable for most patients. Proteins are produced in the body via messenger RNA (mRNA) translation. This process can be readily replicated through administering a chemical nucleic acid product to manufacture the same protein recombinantly. The progress made in creating these proteins ex vivo in a cell-free system also offers a lower-cost option to produce therapeutic proteins. This article compares these alternative methods for recombinant protein production, assessing their respective advantages and limitations. While developers and regulatory agencies may encounter significant challenges in navigating product approval, including many unresolved intellectual property issues, these technologies are now proven and offer the most logical solution to making therapeutic proteins accessible to most patients. Full article

(This article belongs to the Section Protein Therapeutics)

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13 pages, 286 KiB

Open AccessReview

The Role of Anti-DFS70 in the Diagnosis of Systemic Autoimmune Rheumatic Diseases

by Liudmila Zotova, Victoria Kotova and Zakhar Kuznetsov

Biologics 2023, 3(4), 342-354; https://doi.org/10.3390/biologics3040019 - 14 Nov 2023

Viewed by 6861

Abstract

The diagnosis of systemic autoimmune rheumatic disease (SARD) or its exclusion is carried out taking into account the results of immunological studies, primarily antinuclear antibodies (ANA) and specific autoantibodies. Often, during ANA analysis via indirect immunofluorescence reaction on cellular and tissue substrates, a [...] Read more.

The diagnosis of systemic autoimmune rheumatic disease (SARD) or its exclusion is carried out taking into account the results of immunological studies, primarily antinuclear antibodies (ANA) and specific autoantibodies. Often, during ANA analysis via indirect immunofluorescence reaction on cellular and tissue substrates, a dense fine speckled 70 (DFS70) fluorescence pattern is observed. Studies on the diagnostic significance of antibodies to anti-DFS70 allow for optimizing the stepwise diagnosis of SARD. Currently, a two-step strategy for laboratory diagnostic investigation is recommended: in the first step, ANA screening is performed, and in the second step, patients with positive results undergo confirmatory tests to detect specific antibodies against individual nuclear antigens. The detection of anti-DFS70 in ANA-seropositive patients without clinical and/or other specific serological markers characteristic of a particular disease within the SARD group may be considered a negative prognostic marker. Also, in the process of decision making in clinical practice, we should remember that anti-DFS70 can be found in the blood of patients with a different, non-SARD pathology and that most people showing anti-DFS70 are healthy individuals. Full article

(This article belongs to the Section Diagnostics)

7 pages, 639 KiB

Open AccessCase Report

Is Metagenomics the Future Routine Diagnosis Tool for Brain Abscesses? About a Case

by William Lars, Claudie Lamoureux, Jérémy Picard, Christophe Rodriguez, Clémence Beauruelle, Luc Quaesaet, Geneviève Héry-Arnaud, Séverine Ansart and Anne Coste

Biologics 2023, 3(4), 335-341; https://doi.org/10.3390/biologics3040018 - 27 Oct 2023

Cited by 1 | Viewed by 1665

Abstract

Shotgun metagenomics (SMg) usefulness for brain abscess diagnosis is not known. We describe a case of brain abscess diagnosed with SMg and provide a review of the literature. A 70-year-old woman was diagnosed with multiple brain abscesses. Standard culture techniques and 16S rRNA [...] Read more.

Shotgun metagenomics (SMg) usefulness for brain abscess diagnosis is not known. We describe a case of brain abscess diagnosed with SMg and provide a review of the literature. A 70-year-old woman was diagnosed with multiple brain abscesses. Standard culture techniques and 16S rRNA gene sequencing of abscess samples remained negative. SMg finally revealed the presence of sequences from Streptococcus anginosus and Fusobacterium nucleatum, leading to antimicrobial treatment adaptation and corticosteroids initiation. The patient finally recovered. A literature review retrieved fifteen other cases of brain abscesses diagnosed with SMg. SMg results led to changes in patient management in most cases. The existing literature about the performances of SMg, its advantages, future evolutions, and limitations is then discussed. SMg place in routine should be evaluated and defined through prospective studies. Full article

(This article belongs to the Section Diagnostics)

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14 pages, 805 KiB

Open AccessReview

Neoantigens: The Novel Precision Cancer Immunotherapy

by Tiantian Zhang, Esaw Kurban and Zhe Wang

Biologics 2023, 3(4), 321-334; https://doi.org/10.3390/biologics3040017 - 18 Oct 2023

Viewed by 4755

Abstract

The past few decades have witnessed the remarkable progress of cancer immunotherapy. Neoantigens, also known as tumor-specific antigens, are novel antigens originating from tumor-specific alterations such as genomic mutations, dysregulated RNA splicing, and post-translational modifications. Neoantigens, recognized as non-self entities, trigger immune responses [...] Read more.

The past few decades have witnessed the remarkable progress of cancer immunotherapy. Neoantigens, also known as tumor-specific antigens, are novel antigens originating from tumor-specific alterations such as genomic mutations, dysregulated RNA splicing, and post-translational modifications. Neoantigens, recognized as non-self entities, trigger immune responses that evade central and peripheral tolerance mechanisms. With the notable strides in cancer genomics facilitated by next-generation sequencing technologies, neoantigens have emerged as a promising avenue for tumor-specific immunotherapy grounded in genomic profiling-based precision medicine. Furthermore, a growing number of preclinical and clinical investigations are harnessing the potential synergies between neoantigens and other immunotherapies such as adoptive cell therapy and immune checkpoint inhibitors. In this review, we will provide a comprehensive perspective encompassing the trajectory of neoantigens, neoantigen design strategies, and the diverse array of clinical applications inherent in immunotherapy strategies centered around neoantigens. Moreover, we delve into the inherent prospects and challenges that accompany the clinical adoption of neoantigen-based immunotherapies while also putting forth potential solutions to address these challenges. Full article

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13 pages, 879 KiB

Open AccessArticle

Dose-Dependency of the Glycemic Response to Polyphenol-Rich Sugarcane Extract (PRSE)

by Matthew Flavel, Julian Neoh and Kosta Fremielle Lim

Biologics 2023, 3(4), 308-320; https://doi.org/10.3390/biologics3040016 - 10 Oct 2023

Cited by 1 | Viewed by 2693

Abstract

Foods high in available carbohydrates, such as plain white sugar or sucrose, increase the postprandial blood glucose levels that may aggravate the risk of developing Type 2 Diabetes. One class of compounds that is gaining popularity due to its potential application in reducing [...] Read more.

Foods high in available carbohydrates, such as plain white sugar or sucrose, increase the postprandial blood glucose levels that may aggravate the risk of developing Type 2 Diabetes. One class of compounds that is gaining popularity due to its potential application in reducing the release of sugars for absorption into the body is polyphenols. The study aimed to investigate the effect of adding different doses of polyphenol-rich sugarcane extract (PRSE) to sucrose to lower the postprandial glycemia of the participants in a non-randomized study. The four test samples’ Glycemic Index (GI) values were calculated based on the standardized recommended methodology by comparing the area under the curve (AUC) of the test samples against the glucose standard. The glucose concentration curves were similar for the four test foods. The glucose response curves, and GI values were decreased in a dose-dependent manner. The results of this study indicate that PRSE-coated sugar can lower postprandial glycemia in normal individuals. Additionally, decreasing GI values with an increasing concentration of polyphenols suggests a dose-dependent effect between polyphenol levels and GI. Full article

(This article belongs to the Section Natural Products)

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12 pages, 1079 KiB

Open AccessArticle

Robust Porcine GFR Measurement with Radiotracers and Only Late Blood Samples

by Lars Jødal, Juan Ignacio Brignone, Pui-Ki Chan Ladefoged, Lars Lund and Trine Borup Andersen

Biologics 2023, 3(4), 296-307; https://doi.org/10.3390/biologics3040015 - 29 Sep 2023

Viewed by 1629

Abstract

(1) Pigs are physiologically very relevant as animal models of human physiology. Radiotracer methods for porcine GFR (glomerular filtration rate) determination exist but require full-curve blood sampling or the application of correction formulas, which vary among studies. (2) We used porcine GFR data [...] Read more.

(1) Pigs are physiologically very relevant as animal models of human physiology. Radiotracer methods for porcine GFR (glomerular filtration rate) determination exist but require full-curve blood sampling or the application of correction formulas, which vary among studies. (2) We used porcine GFR data (40 datapoints from 20 juvenile pigs) for which the GFR was measured as the plasma clearance of [^99mTc]Tc-DTPA. The reference clearance (Cl, GFR; range 41–85 mL/min) was measured from the full curve under the data. For simpler determination, an approximate clearance, Cl₁, was based on the last five blood samples (acquired 120–240 min post injection). (3) The following formula for the GFR was developed: Cl = 1.27 · (Cl₁)^0.92. The spread (SD) was within 4% of the reference GFR. A comparison with the literature data showed that our correction formula was robust in pigs of various breeds, sizes up to approximately 200 kg, and GFRs up to approximately 400 mL/min, with a spread of up to 8%. The formula was also applicable for iohexol as the tracer. (4) A formula was developed that allows porcine GFR to be measured using only 4–5 late blood samples. This new formula can be applied across a wide range of swine breeds, animal sizes, and GFR ranges, allowing for robust determination of the GFR in pigs without full-curve blood sampling and without urine collection. Full article

(This article belongs to the Section Diagnostics)

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43 pages, 2274 KiB

Open AccessReview

The Dawn of In Vivo Gene Editing Era: A Revolution in the Making

by Sarfaraz K. Niazi

Biologics 2023, 3(4), 253-295; https://doi.org/10.3390/biologics3040014 - 25 Sep 2023

Cited by 2 | Viewed by 6694

Abstract

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a “normal” version of the gene into the body while the diseased gene remains in the [...] Read more.

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a “normal” version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no in vivo GE product has been approved, as opposed to 22 GT products approved by the FDA, and many more are under development. No GE product has been approved globally; however, critical regulatory agencies are encouraging their entry, as evidenced by the FDA issuing a guideline specific to GE products. The potential of GE in treating diseases far supersedes any other modality conceived in history. Still, it also presents unparalleled risks—from off-target impact, delivery consistency and long-term effects of gene-fixing leading to designer babies and species transformation that will keep the bar high for the approval of these products. These challenges will come to the light of resolution only after the FDA begins approving them and opening the door to a revolution in treating hundreds of untreatable diseases that will be tantamount to a revolution in the making. This article brings a perspective and a future analysis of GE to educate and motivate developers to expand GE products to fulfill the needs of patients. Full article

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Biologics, Volume 3, Issue 4 (December 2023) – 9 articles

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