Treatment of leukemia antigen-loss relapses occurring after CD19-targeted immunotherapies by combination of anti-CD123 and anti-CD19 chimeric antigen receptor T cells

• Published in: Journal for immunotherapy of cancer Vol. 3; no. Suppl 2; p. O5
• Main Authors: Ruella, Marco, Barrett, David M, Kenderian, Saad S, Shestova, Olga, Hofmann, Ted J, Scholler, John, Lacey, Simon F, Melenhorst, Jan J, Nazimuddin, Farzana, Perazzelli, Jessica, Christian, David A, Hunter, Christopher A, Porter, David L, June, Carl H, Grupp, Stephan A, Gill, Saar
• Format: Journal Article
• Language: English
• Published: London BioMed Central 04.11.2015; BMJ Publishing Group LTD
• Subjects: Antigens; Cancer; Immunology; Immunotherapy; Leukemia; Lymphocytes; Medicine; Medicine & Public Health; Oncology; Oral Presentation; CART19 Treatment; Leukemia Stem Cell; Acute Myeloid Leukemia; CART123 Cell; Chimeric Antigen Receptor
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1186/2051-1426-3-S2-O5

The goal of this study was to pre-clinically evaluate the impact of targeting both CD19 and CD123 with chimeric antigen receptor T cells for the treatment and prevention of CD19-negative relapses occurring after CD19-directed therapies [4, 5]. CD123 was highly expressed (81.75%, range: 5.10-99.60), representing a promising candidate for targeted therapy in B-ALL. [...]CD123 was also found to be expressed in the putative leukemia stem cells, identified as CD34-pos CD38-neg. The expression of CD123 was detected in all (n=6) CD19-negative B-ALL blasts analyzed after relapse from CART19 treatment (representative case in Figure 1). [...]we generated anti-CD123 chimeric antigen receptor T cells co-stimulated with 4-1-BB using a lentiviral vector (CART123) [5].