PD‐1 blocking antibodies moonlighting as killers

Structural biology of moonlighting: lessons from antibodies.

Protein moonlighting is the property of a number of proteins to have more than one function. However, the definition of moonlighting is somewhat imprecise with different interpretations of the phenomenon. True moonlighting occurs when an individual evolutionary protein domain has one well-accepted role and a secondary unrelated function. The 'function' of a protein domain can be defined at diff...

Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy

Immune-checkpoint blocking antibodies have demonstrated objective antitumor responses in multiple tumor types including melanoma, non-small cell lung cancer (NSCLC), and renal cell cancer (RCC). In melanoma, an increase in overall survival has been demonstrated with anti-CTLA-4 and PD-1 inhibition. However, a plethora of immune-mediated adverse events has been reported with these agents. Immune...

A Case of Immune Thrombocytopenia as a Rare Side Effect of an Immunotherapy with PD1-Blocking Agents for Metastatic Melanoma.

Background Checkpoint blocking agents such as pembrolizumab or nivolumab may induce a diversity of mostly autoimmune-mediated side effects. These autoimmune phenomena mainly affect ductless glands such as the pituitary gland (hypophysitis), the thyroid gland (thyreoiditis), the skin (vitiligo and rash), the colon (colitis), and the lung (pneumonitis). Furthermore, many other organs or organ sys...

Dendritic Cells as Killers: Mechanistic Aspects

Blocking PD1-ligand in vitro causes the expansion of Tregs suggesting the mechanism