Hot Molecules for Immunotherapy

Hot Molecules for Immunotherapy: PD-1

PD1, a type 1 transmembrane protein of the Ig superfamily, consists of an extracellular N-terminal IgV-like domain, a transmembrane domain, and a cytoplasmic tail engaging in inhibitory signal transmission. Being expressed on activated immune cell types including T cells, B cells, natural killer (NK) cells, NKT cells, dendritic cells (DCs), macrophages, and host tissues, the expression on effector T cells is associated with constitutive antigen exposure and thus PD1 has become a marker of T cell unresponsiveness or exhaustion.

Hot Molecules for Immunotherapy: CTLA-4

CTLA-4, the first immune checkpoint receptor to be clinically targeted, is expressed exclusively on T cells where it primarily regulates the amplitude of the early stages of T cell activation. Although the exact mechanisms of CTLA-4 action are under considerable debate, it has been proposed that its expression on the surface of T cells dampens the activation of T cells by outcompeting CD28 in binding CD80 and CD86. CD28 signalling strongly amplifies TCR signalling to activate T cells. CD28 and CTLA-4 / CD152 share identical ligands: CD80 and CD86.

Hot Molecules for Immunotherapy: CD20

CD20 (human B-lymphocyte-restricted differentiation antigen, Bp35), is a hydrophobic transmembrane protein with a molecular weight of approximately 35 kD located on pre-B and mature B lymphocytes. The antigen is expressed on most B-cell non-Hodgkin's lymphomas but is not found on stem cells, pro-B cells, normal plasma cells or other normal tissues. Plasma blasts and stimulated plasma cells may express CD20. CD20 regulates an early step(s) in the activation process for cell cycle initiation and differentiation, and possibly functions as a calciumion channel. CD20 is not shed from the cell surface and does not internalize upon antibody binding. Free CD20 antigen is not found in the circulation; thus a drug that reacts with CD20, such as an antibody, would not be neutralized before binding to its target cell.