Immunotherapy

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🌱 來自: Huppert’s Notes

Immunotherapy🚧 施工中

Immunotherapy

•   Mechanism: Checkpoint inhibitors enable the patient’s own immune system to better target and destroy malignant cells by blocking the signals that turn the immune system off. In other words, they release the brakes on the immune response so that the immune system can more effectively fight malignancy (Figure 7.9).

FIGURE 7.9: Mechanism of T cell activation and inhibition and the role of checkpoint inhibitor therapy. T cell activation is mediated by the interaction of the T cell receptor with the major histocompatibility complex (MHC) and the CD28 receptor with the B7 co-stimulatory molecule on the antigen presenting cell (APC). T cell inhibition is mediated by the interaction of PD-L1 and PD-1 as well as CTLA-4 and B7. Inhibitors of PD-1, PD-L1, and CTLA-4 prevent the inactivation of T cells, thus allowing the T cells to destroy the tumor cell more effectively. Activating interactions are noted with a (+) and inhibitory interactions are noted with a (-). Examples of check point inhibitors (CPIs) are listed above. Abbreviations: Antigen presenting cell (APC), major histocompatibility complex (MHC), programmed death receptor-1 (PD-1), programmed death receptor ligand-1 (PD-L1), cytotoxic T lymphocyte-associated protein 4 (CTLA-4).

•   Indications: Approved for multiple types of cancer (e.g., melanoma, RCC, NSCLC, HCC, and now many more tumor types). PD-1 inhibitors are the first class of drugs with an FDA approval for a genetic pattern rather than an anatomical site (FDA approved for microsatellite instability [MSI]-high or mismatch repair deficient cancers and tumor mutational burden [TMB]-high cancers).

•   Examples of checkpoint inhibitors by mechanism:

-   Anti-PD1

•   Nivolumab (Opdivo)

•   Pembrolizumab (Keytruda)

-   Anti-PD-L1

•   Atezolizumab (Tecentriq)

•   Avelumab (Bavencio)

•   Durvalumab (Imfinzi)

-   Anti-CTLA4

•   Ipilimumab (Yervoy)

•   Side effects:

-   Immune-related adverse events (IRAEs): Autoimmune side effects due to excessive immune system activation

•   Most common: Thyroid disease, colitis, hepatitis, rashes

•   Less common but more serious: Hypophysitis, pneumonitis, myocarditis, myositis, neurologic autoimmune processes

-   Timing: IRAEs usually develop within the first few weeks to months after treatment initiation, but can occur at any time during or after treatment

-   Treatment: Depending on the grade of toxicity (See ASCO/NCCN guidelines), sometimes can treat through and other times need to stop immunotherapy and provide immunosuppression.