Good news! Cancer is history (soon)! What seems very significant here is that this approach can be used to treat solid tumors.
Though, I have a little trouble to understand how that would exactly work in context of cancer treatment. The headlines are perhaps overpromising.
"... Researchers ... believe they have identified a protein on a receptor that can "program" cancer cells to die.
The press release ... states: "CD95 receptors, also known as Fas, are called death receptors. These protein receptors reside on cell membranes. When activated, they release a signal that causes the cells to self-destruct." ..."
"... "... But most importantly, this sets the stage to develop antibodies that activate Fas, selectively kill tumor cells, and potentially support CAR T-cell therapy in solid tumors.” ..."
From the abstract:
"Receptor clustering is the most critical step to activate extrinsic apoptosis by death receptors belonging to the TNF superfamily. Although clinically unsuccessful, using agonist antibodies, the death receptors-5 remains extensively studied from a cancer therapeutics perspective. However, despite its regulatory role and elevated function in ovarian and other solid tumors, another tumor-enriched death receptor called Fas (CD95) remained undervalued in cancer immunotherapy until recently, when its role in off-target tumor killing by CAR-T therapies was imperative. By comprehensively analyzing structure studies in the context of the binding epitope of FasL and various preclinical Fas agonist antibodies, we characterize a highly significant patch of positively charged residue epitope (PPCR) in its cysteine-rich domain 2 of Fas. PPCR engagement is indispensable for superior Fas agonist signaling and CAR-T bystander function in ovarian tumor models. A single-point mutation in FasL or Fas that interferes with the PPCR engagement inhibited apoptotic signaling in tumor cells and T cells. Furthermore, considering that clinical and immunological features of the autoimmune lymphoproliferative syndrome (ALPS) are directly attributed to homozygous mutations in FasL, we reveal differential mechanistic details of FasL/Fas clustering at the PPCR interface compared to described ALPS mutations. As Fas-mediated bystander killing remains vital to the success of CAR-T therapies in tumors, our findings highlight the therapeutic analytical design for potentially effective Fas-targeting strategies using death agonism to improve cancer immunotherapy in ovarian and other solid tumors."
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