PIK3CD гені және иммундық қатерсіздік ауруларына емдік әсері

Protein coding gene in the species Homo sapiens

Phosphatidylinositol 4,5 bisphosphate 3 kinase catalytic subunit delta isoform also known as phosphoinositide 3 kinase (PI3K) delta isoform or p110δ is an enzyme that in humans is encoded by the PIK3CD gene.

Inherited mutations in the PIK3CD gene which increase p110δ catalytic activity cause a primary immunodeficiency syndrome called APDS or PASLI.

US pharmaceutical company ICOS produced a selective inhibitor of p110δ called IC87114. This inhibitor selectively impairs B cell, mast cell and neutrophil functions and is therefore a potential immune modulator. The p110δ inhibitor idelalisib was developed by Gilead Sciences. Idelalisib in combination with rituximab showed favourable progression free survival in a phase III clinical trial for chronic lymphocytic leukemia (CLL) compared with patients that received rituximab and placebo. In July 2014 idelalisib was approved by the FDA as a treatment for CLL patients. In September 2017 copanlisib, inhibiting predominantly p110α and p110δ, got FDA approval for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies. In September 2018 duvelisib was approved by the FDA as a treatment for relapsed or refractory CLL, and relapsed follicular lymphoma (FL) patients, who have received at least two prior therapies. A 2015 study found that p110δ inhibitors had a side effect of boosting mouse immune responses against multiple cancers, including both solid and hematological types. Breast cancer mice survival times nearly doubled and spread significantly less, with far fewer and smaller tumors. Post surgical survival also improved. Subject immune systems could also develop an effective memory response, extending protection. p110δ inactivation in regulatory T cells unleashes CD8+ cytotoxic T cells.