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Co-STAR Cells: A Breakthrough in Cancer Immunotherapy
Context; Investigators at the Johns Hopkins Kimmel Cancer Center and its Ludwig Center, the Lustgarten Laboratory, and Bloomberg~Kimmel Institute for Cancer Immunotherapy have designed a novel type of cell to recognize and fight cancer.
Genetic Engineering Techniques:
- These cells are called Co-STAR (Co-stimulatory Synthetic T-cell receptor and Antigen Receptor) cells.
- Researchers combined genetic components of four types of cells to create Co-STAR cells:
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- T-cell receptors (TCRs) from T cells, Antibodies from B cells, MyD88 from monocytes, CD40 from dendritic and other cells
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- Mechanism of Action;
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- The TCR and antibody components act as an “invader-detecting device,” recognizing cancer cells as foreign.
- The “alarm” triggered by this hybrid detector is boosted by the MyD88 and CD40 components.
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- The T-cell receptor (TCR): It is a complex of integral membrane proteins that is found on the surface of T cells and is responsible for recognizing antigens bound to major histocompatibility complex (MHC) molecules.
- Antibodies are protective proteins produced by B cells (also known as B lymphocytes) that play a crucial role in the humoral immune response.
- MyD88 (Myeloid Differentiation primary response gene 88): It is an adapter protein that plays a crucial role in the activation of innate immune cells, particularly monocytes, through Toll-like receptor (TLR) signalling.
- CD40: It is a critical receptor expressed on dendritic cells and other antigen-presenting cells that plays a key role in regulating immune responses.
Research Findings:
Antigen:
- Any substance that triggers an immune response. Antigens include toxins, chemicals, bacteria, viruses, and other external substances.
- Body tissues and cells, including cancer cells, also have antigens.
- Laboratory Studies: Co-STARs led to a sustained anti-tumor response against human cancer cells growing in test tubes.
- Animal Studies: Co-STARs induced robust, long-lasting proliferation of T cells in mouse models, leading to profound remissions and often curing human cancer cells growing in mice.
- Traditional T cells or CAR T cells could not eradicate cancer cells in vitro and only temporarily controlled tumours in mice.
- Surprised success in mice, having generated many types of T cells over four years that only slows cancer growth.
Specific Antigen Targeting:
- Peptide-HLA Antigens: Target specific antigens such as peptide fragments from mutant proteins inside the cancer cell displayed on the cell surface by HLAs.
- Challenge: These antigens are present in very low numbers in a cancer cell, and classic CAR format cannot react to such a small amount.
About CAR T-cell Therapy:
- It is a type of immunotherapy that uses a patient’s own T cells (a type of immune system cell) that have been genetically modified to recognize and attack cancer cells.
- CAR stands for “chimeric antigen receptor,” a synthetic receptor added to the patient’s T cells to help them recognize and bind to specific antigens on cancer cells.
- The process involves collecting the patient’s T cells, genetically engineering them to produce CAR, and infusing the modified “CAR T cells” back into the patient.
- CAR T cells target and attack cancer cells expressing the specific antigen, such as CD19 on B-cell cancers.
- Once infused, CAR T cells multiply and continue to seek out and destroy cancer cells, acting as a “living drug.”
- CAR T-cell therapy has shown promising results in treating certain blood cancers, like some types of leukaemia and lymphoma, when other treatments have failed.