Checkpoint inhibitors ensure that cancer cells cannot switch off the attack by the body’s own immune cells. Our body’s own defense system (immune system) serves to protect against diseases. It becomes active, for example, when there is an infection with pathogens such as bacteria or viruses (immune reaction).
But it is also of great importance for the fight against cancer cells. Certain defense cells (the so-called T cells) are particularly important. Under certain conditions, they can recognize and destroy cancer cells. With many immune reactions it is important that they stop after the cause has been eliminated (e.g. when an infection has subsided). That is why there are so-called receptors on certain cells of the immune system that are responsible for controlling the immune response.
In simplified terms, these receptors can be thought of as switches that activate or deactivate cells of the immune system. The switches for the T cells are called checkpoint receptors. Cancer cells can bind to the checkpoint receptors and thus switch off the T cells. In this way, the cancer cells escape the attack of the immune system or at least weaken it. Checkpoint inhibitors are special proteins (antibodies) that prevent cancer cells from attaching to the checkpoint receptors. They can also increase the activation of T cells. The T cells remain activated and can fight the cancer cells better. That is why checkpoint inhibitors are used as drugs to treat certain cancers.
However, checkpoint inhibitors can cause other immune reactions in the body to be more violent. Checkpoint inhibitors are given as an intravenous infusion. They can be administered alone (as monotherapy) or in combination with other drugs such as cytostatics.
Immunotherapy for cancer patients is currently experiencing a renaissance worldwide. It is no longer just chemotherapy or radiation that is decisive for the healing success of an oncological therapy, but increasingly also immunotherapy. In particular, the recently internationally approved substances (PDL-1 / PD-1 and CTL-4 antibodies) have currently achieved a breakthrough in oncology in indications that were previously considered completely incurable. Approvals for malignant melanoma, kidney cell and lung cancer have already been granted and approvals for other indications are expected shortly.
We have found that the combination of these checkpoint inhibitors with hyperthermia and an immunotherapy that has been established worldwide for 30 years shows particularly good results: We combine the aforementioned checkpoint inhibitors with local hyperthermia and whole-body hyperthermia as well as interleukin-2 (IL-2) . The safety and tolerability of this method was published in 2006 by the group of Prof. Redmond at Cork University in Ireland.
We successfully published the first very promising interim results of this immunotherapy in 2016 as abstracts at the American cancer society ASCO and the European cancer society EORTC.
In the 1990s, James Allison was working on T cells at the University of California at Berkeley. He discovered that the T-cell surface protein CTLA-4 (Cytotoxic T-Lymphocyte-Associated Protein 4) acts as a brake on T-cells. Other research groups used this finding to develop an approach to treating autoimmune diseases. Allison had a different goal:
He wanted to release the brakes and thereby activate the immune system in order to be able to take action against tumor cells.
Expression analysis of the immune checkpoints
Mechanism of action of the checkpoint inhibitors: T cells interact with different cells via surface proteins (receptors). They receive activating signals through the binding of the T cell receptor (TCR) to MHC-I or MHC-II and through the binding of CD28 to CD80.
In contrast, the binding of PD-1 to PD-L1 and of CTLA-4 to CD80 give inhibiting signals. The checkpoint inhibitors ipilimumab, nivolumab or pembrolizumab each delete one of the two inhibiting signals so that the activation of the T cells predominates.
Clinical Studies, Publications & Sources – Here
🎬 The Unbelievable Plight of Mrs. Wright (2019)
It is an honor for us to be part of this success story. It is difficult for us to put into words the mileage that has been set here. The therapy mentioned above contributed to this. Thanks to Grow Vision and our dear Dr. Diana Wright.
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