Professor University of Pennsylvania Philadelphia, Pennsylvania, United States
Disclosure(s):
Nicola Mason, BVM, PhD, DACVIM (SAIM): No relevant disclosure to display
CD19 is a 95kDa transmembrane glycoprotein molecule belonging to the immunoglobulin superfamily. It is expressed on the surface of B cells, from the late pro B cell stage through to the early plasmablast. It functions as a B cell co-receptor, assembling with CD21 and CD81 to decrease the threshold for antigen-specific, B cell receptor dependent stimulation. In humans, most B cell malignancies express CD19 and it is frequently exploited as a direct target for immune based therapies. For example, the use of CD19 re-directed chimeric antigen receptor T cells (CART-19) has produced remarkable results in the treatment of hematological malignancies including acute lymphoblastic leukemia (ALL) chronic lymphocytic leukemia (CLL) and B cell NHL. The combination of a CD19 targeting antibody with an agonistic anti-CD3 antibody has produced a Bispecific T cell Engager molecule (or BiTE) known as blinatumomab, which is FDA approved for the treatment of human relapsed or refractory ALL. Anti-CD19 antibody drug conjugates are also showing promise in the treatment of B cell malignancies in the human clinic. In addition, targeting CD19 using CAR-T cells (CART-19) has recently shown remarkable success in the treatment of autoimmune diseases including SLE and inflammatory myositis in human patients. In these patients, CART-19 eliminated B cells and plasmablasts, reduced levels of autoantibody and increases complement levels in the periphery. Furthermore, the B cells that emerged following CART-19 therapy were naïve by flow cytometry, suggesting that CART-19 therapy can essentially re-set the B cell immune repertoire, eliminate auto-reactive clones, and providing long term remission from autoimmunity. In this lecture, we will discuss the value of CD19 as a target, the various different immunotherapeutic strategies that are being used to target CD19 in the human clinics and we will discuss the current state of CD19 targeted immune therapies for use in canine oncology and internal medicine.
Learning Objectives:
Upon completion, participant will be able to describe the function and cellular distribution of CD19
Upon completion, participant will be able to describe 4 different immunotherapeutic strategies to eliminate CD19+ B cells and plasmablasts and the advantages and disadvantages of each approach
Upon completion, participant will be able to describe what a chimeric anitgen receptor (CAR)-T cell is, how it is made and ways in which it can be engineered to improve its function and persistence and the adverse effects and mechanisms of tumor escape after CART-19 therapy
