Novel targets for immune-checkpoint inhibition in cancer

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

Treatment of cancer

This patent on CRLX-101, an experimental approach using camptothecin (CPT) to cancer chemotherapy, reminded us of a wonderful idea from Mark Davis (Caltech). In CRLX101, CPT is linked covalently through a glycine link to the linear copolymer CDP, which in turn consists of alternating subunits of beta-cyclodextrin and polyethylene glycol (PEG). The CRLX101 nanoparticle is water-soluble. After intravenous injection, active CPT is slowly released as the linkage is hydrolyzed. The size of the nanoparticle (20-50 nm in diameter) facilitates its extravasation in the more leaky vessels of tumors via the enhanced permeability and retention effect. As a result, the anticancer drug is enhanced and retained in the tumor tissue.
The new patent from Ellipses Pharma proposes novel applications dominantly in rectal cancer.
Amato GiacciaHanna SanoffJoel Tepper

Hyaluronan-Cyclodextrin Conjugates as Doxorubicin Delivery Systems

We love both chemistry and carbohydrates. So when people publish about conjugating carbohydrates with carbohydrates and their pharma applications, our hearts are full of inspiration and passion.
Check out how researchers from Università di Catania and Ospedale Policlinico San Martino propose using Hyaluronan-Cyclodextrin Conjugates as drug delivery tools!
Noemi BognanniLuana La PianaSimone Stranorosaria gangemiMaria Teresa CambriaGraziella Vecchio et al

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A bispecific, crosslinking lectibody activates cytotoxic T cells and induces cancer cell death

A fascinating novel concept of cancer research using lectibodies, a bispecific construct composed of a lectin linked to an antibody fragment. This approach aims to redirect the immune system into fighting cancer by targeting altered glycans at the surface of malignant cells.
The University of Freiburgacib GmbH – Francesca RosatoRajeev P.Jana TomischAna Valeria Meléndez MayorgaDajana Kolanovic, Olga Makshakova, Birgit Wiltschi, Winfried Römer 

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Palleon Pharmaceuticals announces issuance of a U.S. Patent for the use of antibody sialidase conjugates

We are always thrilled to see companies adjancing drugs in the field of glycochemistry, just as Palleon Pharmaceuticals. who recently announced patenting engineered human sialidase enzymes that restore antitumor immunity by degrading immunosuppressive sialoglycans on tumors and across immune cell types

Press releases