Novel targets for immune-checkpoint inhibition in cancer

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Immune-checkpoint inhibitors have revolutionized cancer therapy, yet many patients either do not derive any benefit from treatment or develop a resistance to checkpoint inhibitors. Intrinsic resistance can result from neoantigen depletion, defective antigen presentation, PD-L1 downregulation, immune-checkpoint ligand upregulation, immunosuppression, and tumor cell phenotypic changes. On the other hand, extrinsic resistance involves acquired upregulation of inhibitory immune-checkpoints, leading to T-cell exhaustion. Current data suggest that PD-1, CTLA-4, and LAG-3 upregulation limits the efficacy of single-agent immune-checkpoint inhibitors. Ongoing clinical trials are investigating novel immune-checkpoint targets to avoid or overcome resistance. This review provides an in-depth analysis of the evolving landscape of potentially targetable immune-checkpoints in cancer, highlight their biology, emphasizes the current understanding of resistance mechanisms, and focuses on promising strategies that are under investigation. Current results and ongoing clinical trials in this crucial field that could once again revolutionize outcomes for cancer patients are also collected.

Novel targets for immune-checkpoint inhibition in cancer – Cancer Treatment Reviews

The multifaceted roles of galectins: glycan-binding proteins with multiple personalities

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Galectins are an evolutionarily conserved family of glycan-binding proteins with multifunctional roles in immunity. These proteins often shuttle between different intracellular compartments (nucleus, cytoplasm, and organelles) and are released to the extracellular milieu, where they acquire different roles in response to diverse microenvironmental stimuli, including hypoxia, nutrient availability, intracellular and extracellular pH, cytokine milieu and the presence of proinflammatory or immunosuppressive signals. Within the immune system, galectins can elicit a wide array of important functions that tailor both innate and adaptive responses, playing key roles in shaping the choreography of immune cells in health and disease. Interestingly, the same galectin can function as a cytokine, chemokine, cell adhesion molecule, immune checkpoint molecule, danger-associated molecular pattern, or growth factor depending on different cellular programs, including activation, differentiation, and trafficking, or during pathologic conditions, such as pathogen invasion, autoimmune inflammation, fibrosis and cancer.
Learn more from the great white paper by Gabriel Rabinovich!

The multifaceted roles of galectins: glycan-binding proteins with multiple personalities (glycoforum.gr.jp)

Bioresponsive and multifunctional cyclodextrin-based non-viral nanocomplexes in cancer therapy: Building foundations for gene and drug delivery, immunotherapy and bioimaging

carbohydrates

The interest in application of nanomaterials in the field of cancer therapy is that the drawbacks of conventional therapies, including chemoresistance, radio-resistance and lack of specific targeting of tumor cells can be solved by nanotechnology. 
The application of cyclodextrin in cancer shows an increasing trend due to the benefits of these nano complexes in improving the solubility and bioavailability of current bioactives and therapeutics for cancer. CDs are widely utilized in the delivery of drugs and genes in cancer therapy, and by targeted delivery of these therapeutics into target sites, they improve anti-proliferative and anti-cancer potential.
Great review!

See the full article at the following link!

The microbiome and human cancer

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A review in Science Magazine by Greg Sepich-Poore, Ph.D. et al. looked at research that shows how bacteria, viruses and fungi of the microbiome are pervasive among human cancers, are key actors in cancer immunotherapy, and are potentially engineerable to treat metastases. Advances in microbiome research are improving our understanding of immuno-oncology and driving new diagnostic and therapeutic approaches.

Check out the article at the following link.


Smaller size packs a stronger punch – Recent advances in small antibody fragments targeting tumour-associated carbohydrate antigens

carbohydrates,

Very educative review on recent advances in small antibody fragments targeting tumor-associated carbohydrate antigens
Glycans represent the most versatile post-translational modification in nature and surround all human cells. Unique glycan structures are monitored by the immune system and differentiate self from non-self and healthy from malignant cells. Aberrant glycosylations, termed tumor-associated carbohydrate antigens (TACAs), are a hallmark of cancer and are correlated with all aspects of cancer biology. Therefore, TACAs represent attractive targets for monoclonal antibodies for cancer diagnosis and therapy. However, due to the thick and dense glycocalyx as well as the tumor micro-environment, conventional antibodies often suffer from restricted access and limited effectiveness in vivo. To overcome this issue, many small antibody fragments have come forth, showing similar affinity with better efficiency than their full-length counterparts. In this paper, small antibody fragments against specific glycans on tumour cells and highlighting their advantages over conventional antibodies are presented.
Sana Khan Khilji, Charlotte Op ‘t Hoog, David Warschkau, Felix Goerdeler, Anika Freitag, Peter Seeberger, Oren Moscovitz

See the article here

Co-Delivery of 8-Hydroxyquinoline Glycoconjugates and Doxorubicin by Supramolecular Hydrogel Based on α-Cyclodextrin and pH-Responsive Micelles for Enhanced Tumor Treatment

drug delivery, ,

Two birds with one stone:
This study of the Silesian University of Technology and the Polish Academy of Sciences is close to our hearts as we both deal with glycoconjugates and cyclodextrin. They show the delivery of 8-Hydroxyquinoline Glycoconjugates and Doxorubicin using ACD-based hydrogel for enhanced tumor treatment.

Monika D. Gabriela Pastuch Piotr Kurcok 

See the full article here

Genetically encoded chemical crosslinking of carbohydrate

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Covalent linkages are engineered between proteins and carbohydrates under biocompatible conditions. Genetically encoding the chemical crosslinking of proteins to carbohydrates offers a solution to address the low affinity and weak strength of protein–sugar interactions.
The University of California, San Francisco – Shanshan Li, Nanxi Wang, Bingchen Yu Wei Sun Lei Wang present pure beauty!
Read the full article on nature.com

carbohydrate, carbohyde, gene encode

The choanoflagellate pore-forming lectin SaroL-1 punches holes in cancer cells by targeting the tumor-related glycosphingolipid Gb3

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Great read on pore-forming lectin SaroL-1 punching holes in cancer cells by targeting the tumor-related glycosphingolipid Gb3 presented by a well-known team led by Anne Imberty (Grenoble University), Winfried Römer (Université de Fribourg – Universität Freiburg) and Frederique Lisacek (University of Geneva)
Fascinating!


#carbohydrates #glycotime #cancerresearch #cancer