A saliva-specific fucosylated structure-based sugar profile

carbohydrates

A saliva-specific fucosylated structure-based sugar profile seems to be an efficent cancer diagnostic tool as claimed by Soochow University.
From the human saliva sample proteins extracted, subjected to enzymolysis and enriched in glycans from glycoproteins. Structural analysis and quantitative analysis of abundance on the glycans by means of mass spectrometry determines a glycan profile in the sample. By analyzing healthy saliva, non-cancer saliva, and lung cancer saliva, sugar profiles of high-abundance core fucose and branched fucose are identified. The method can be applied to clinical screening of lung cancer. The saliva-specific fucosylated structure-based sugar profile and the detection method therefor facilitate early diagnosis, feature easy-to-collect samples, and are not harmful to a patient, and thus have an excellent application prospect and important significance in the aspects of early screening and treatment of high-morbidity and high-death-rate lung cancer.

See the full patent here

Insights into recent preclinical studies on labeled cyclodextrin-based imaging probes: Towards a novel oncological era

Today's cyclodextrin,

today’s cyclodextrin:
is a beautiful review on labeled CD-based imaging probes from University of Debrecen (Zita Képes, István Hajdu, Ferenc Fenyvesi, and György Trencsényi).
As malignancies remain one of the major health concerns worldwide, increasing focus has been centered on the application of cyclodextrins (CDs) in cancer imaging and therapy due to their outstanding inclusion-forming capability. Studies applying fluorescently- CDs, or CD-based MRI contrast agents revealed much about pharmacokinetics and diagnostic applications; however, derivatives labeled with positron emitters seem superior molecular probes in the investigation of the route of CDs in the biological niche. Exploiting the firm signaling interaction between cancer-related cyclooxygenase-2, prostaglandin E2 (PGE2), and RAS oncoprotein, radioconjugated, PGE2-affine CDs project the establishment of novel imaging probes and therapeutic agents. 

See the full article here: Insights into recent preclinical studies on labelled cyclodextrin-based imaging probes: Towards a novel oncological era

Tailoring renal-clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery

drug delivery, Today's cyclodextrin, ,

Today’s cyclodextrin:
Tailoring renal-clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery
Although cyclodextrin-based renal-clearable nanocarriers have a high potential for clinical translation in targeted cancer therapy, their designs remain to be optimized for tumor retention. Here Seoul National University and Chungnam National University report on the design of renal-clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery. The optimized cyclodextrin shows a high tumor accumulation and is used for the delivery of doxorubicin and ulixertinib. Higher tumor accumulation and tumor penetration facilitate tumor elimination. The improved antitumor efficacy is demonstrated in heterotopic and orthotopic colorectal cancer models.

See the full article here: Tailoring renal-clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery

Lipid-based RNA formulations suitable for therapy

Today's cyclodextrin, , , ,

today’s cyclodextrin:
In this invention, BioNTech SE provides a method of producing a composition comprising RNA lipoplex particles. The main focus of the description is antitumoral therapy.
In the formulation itself, the aqueous colloidal suspension of liposomes is combined with an aqueous solution comprising RNA, thereby producing the composition comprising RNA lipoplex particles. The formulation requires frozen storage conditions; hence the use of cyroprotectant is necessary. The invention proposes mono- di- and oligosaccharides to protect such compositions, including various cyclodextrins and cyclodextrin polymers.
The use of cyclodextrins as cryoprotectants and stabilizers in biopharmaceutical formulations is an emerging technology.

Dr. Hossam Hefesha, Heinrich Haas, Ferdia Bates, Christian Hotz
Katalin Karikó

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Three-in-one: exploration of co-encapsulation of cabazitaxel, bicalutamide and chlorin e6 in new mixed cyclodextrin-crosslinked polymers

drug delivery, ,

Another great paper comes out of the long-term collaboration between our CSO,Milo Malanga and Ilse Manet‘s lab at National Research Council of Italy.
We explored a series of cyclodextrin (CyD) polymers composed either of a single CyD type or a mixture of two CyD types to encapsulate simultaneously different compounds with potential therapeutic interest for multimodal prostate cancer treatment. Thanks to a single inexpensive CyD-based polymer, we produced a three-in-one platform for the future implementation of combined chemotherapy and photodynamic therapy. These achievements are most relevant as nanomedicines are continuously proposed, but their potential for translation to the pharma industry is compromised by their limited potential for industrial upscale.

Elisabetta Pancani, PharmD, Marco Agnes, Arianna Mazza, Alessandro Venturini et al.

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The hidden potential of glycomarkers: Glycosylation studies in the service of cancer diagnosis and treatment

carbohydrates, ,

Changes in the glycosylation process appear early in carcinogenesis and evolve with the growth and spread of cancer. The correlation of the characteristic glycosylation signature with the tumor stage and the appropriate therapy choice is important in translational medicine. Oncologists also pay attention to extracellular vesicles as reservoirs of new cancer glycomarkers that can be potent for cancer diagnosis/prognosis. In this review, Karolina Grzesik, Marcelina Janik, Dorota Hoja-Łukowicz from Jagiellonian University collect glycomarkers used in oncology and show their new glycoforms of improved clinical relevance, summarize current knowledge on the biological functions of glycoepitopes in cancer-derived extracellular vesicles and their potential use in clinical practice. Is glycomics a future of cancer diagnosis? It may be but in combination with other omics analyses than alone.

See the full review here: The hidden potential of glycomarkers: Glycosylation studies in the service of cancer diagnosis and treatment


A mannosylated polymer with endosomal release properties for peptide antigen delivery

drug delivery, ,

The University of Washington introduces Man-VIPER, a self-assembling, pH-sensitive, mannosylated polymeric peptide delivery platform that targets dendritic cells in the lymph nodes, encapsulates peptide antigens at physiological pH and facilitates the endosomal release of antigens at acidic endosomal pH through conjugated membranolytic peptide melittin. In vivo, the Man-VIPER polymer demonstrated an adjuvant effect and induced the proliferation of antigen-specific cytotoxic T cells and helper T cells compared to free peptides and Man-AP. The antigen delivery with Man-VIPER-NR generated significantly more antigen-specific cytotoxic T cells than Man-VIPER-R in vivo. and Man-VIPER-NR exerted superior efficacy in a B16F10-OVA tumor model. These results highlight Man-VIPER-NR as a safe and powerful peptide cancer vaccine platform for cancer immunotherapy.

Dinh Chuong (Ben) Nguyen, Tran Luu, Omeed Yazdani, Patrick Stayton and Suzie Pun

See the full article here: A mannosylated polymer with endosomal release properties for peptide antigen delivery

Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia

carbohydrates, drug development, ,

Positive Phase 1/2 clinical data published on uproleselan (GMI-1271), a novel E-selectin antagonist that disrupts cell survival pathways, enhance chemotherapy response, improves survival in mouse xenograft and syngeneic models, and decreases chemotherapy toxicity in vivo.
The addition of uproleselan to chemotherapy was well tolerated, with high remission rates, low induction mortality, and low rates of mucositis, providing a strong rationale for phase 3 randomized confirmatory studies.
Brian Jonas, Jane Jane Liesveld, Dale Bixby, Paula Marlton, John Magnani, Helen Thackray, Eric Feldman, Pamela Becker et al. – GlycoMimetics

See the full clinical trials report here.

Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia