Good news! Cancer is history (soon)!
"... The key to their approach is reversing a “brake” that cancer cells engage to prevent immune cells from launching an attack. This brake is controlled by sugar molecules known as glycans that are found on the surface of cancer cells.
By blocking those glycans with molecules called lectins, the researchers showed they could dramatically boost the immune system’s response to cancer cells. To achieve this, they created multifunctional molecules known as AbLecs, which combine a lectin with a tumor-targeting antibody. ...
Glycans are found on nearly all living cells, but tumor cells often express glycans that are not found on healthy cells, including glycans that contain a monosaccharide called sialic acid. When sialic acids bind to lectin receptors, located on immune cells, it turns on an immunosuppressive pathway in the immune cells. These lectins that bind to sialic acid are known as Siglecs. ...
In this study, the researchers designed an AbLec based on the antibody trastuzumab, which binds to HER2 and is approved as a cancer therapy to treat breast, stomach, and colorectal cancers. To form the AbLec, they replaced one arm of the antibody with a lectin, either Siglec-7 or Siglec-9.
Tests using cells grown in the lab showed that this AbLec rewired immune cells to attack and destroy cancer cells. ..."
From the abstract:
"Despite the curative potential of checkpoint blockade immunotherapy, many patients remain unresponsive to existing treatments.
Glyco-immune checkpoints, which involve interactions of cell-surface glycans with lectin, or glycan-binding, immunoreceptors, have emerged as prominent mechanisms of immune evasion and therapeutic resistance in cancer.
Here, we describe antibody-lectin chimeras (AbLecs), a modular system for glyco-immune checkpoint blockade. AbLecs are bispecific antibody-like molecules comprising a cell-targeting antibody domain and a lectin ‘decoy receptor’ domain that directly binds glycans and blocks their ability to engage inhibitory lectin receptors.
AbLecs potentiate cancer cell destruction by primary human immune cells in vitro and reduce tumour burden in a humanized, immunocompetent mouse model, outperforming most existing therapies and combinations tested.
By targeting a distinct axis of immunological regulation, AbLecs synergize with blockade of established immune checkpoints.
AbLecs can be readily designed to target numerous tumours and immune cell subsets as well as glyco-immune checkpoints, thus representing a potential modality for cancer immunotherapy."
Fig. 1: AbLecs enable targeted glyco-immune checkpoint blockade.
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