Interpretative Information

The successes with chimeric antigen receptor (CAR) T cell therapy involving patients with pre-B cell acute lymphoblastic leukemia (ALL) or B cell lymphomas have revolutionized anticancer therapy, providing a potentially curative option for patients who are refractory to standard treatments. FDA approvals of anti-CD19 CAR T cell products for both ALL and certain types of B cell lymphoma (the first approved gene therapies in the USA). CD19-targeted CAR-T cells, which have been engineered to recognize the CD19 (specifically the FMC63 scFv region) cell surface molecule of malignant B cells, show remarkable efficacy in patients with B cell acute lymphoblastic leukemia. Some patients relapse due to the CAR-T therapy not persisting in the body, leading to antigen loss, tumor escape (frameshift mutation), or exhaustion. 

In the clinical setting, long-term remission in patients with hematological malignancies is associated with sustained persistence of CAR T cells.  In the clinical oncology setting, CAR T cell expansion and persistence correlates with response and attaining remission in patients.  Because of this observation, establishing a reliable and direct method of tracking CAR T cell numbers is particularly important, not only in the estimation of effectiveness of CAR T cell therapy, but in terms of safety evaluation in post-infusion monitoring. Serious side effects of clinical CAR T cell therapy have been noted, one of the most severe being cytokine release syndrome (CRS) and is associated with CAR T cell expansion in vivo.  In addition, a major concern for recipients of allogenic CAR T cells is GvHD.  

The persistence/expansion of CAR T cells is key for determining anti-tumor efficacy, which depends on several factors such as structure of CAR T therapeutic, the manufacturing process, the lymphodepletion regimen, the infused cell phenotype, tumor burden, and disease. Persistence of CAR T-cell population is considered a critical factor of anti-tumor efficacy (therapy effectiveness).  Understanding the limitations of anti-CD19 CAR T cell therapy is critical to realizing the full potential of this treatment approach.  Growing experience with these agents has revealed that remissions will be brief in a substantial number of patients owing to poor CAR T cell persistence and/or cancer cell resistance resulting from antigen loss or modulation.  The Viracor ExPeCT™ anti-CD19 (FMC63) CAR T expansion and persistence assay is a monitoring tool to evaluate and validate the efficacy of anti-CD19 FMC63 CAR T therapy.