T cells expressing CD19-specific Engager Molecules for the Immunotherapy of CD19-positive Malignancies

• Published in: Scientific reports 2016-06, Vol.6 (1), p.27130-27130, Article 27130
• Main Authors: Velasquez, Mireya Paulina, Torres, David, Iwahori, Kota, Kakarla, Sunitha, Arber, Caroline, Rodriguez-Cruz, Tania, Szoor, Arpad, Bonifant, Challice L., Gerken, Claudia, Cooper, Laurence J. N., Song, Xiao-Tong, Gottschalk, Stephen
• Format: Article
• Language: English
• Subjects: 13/106; 13/21; 13/31; 631/67/1990/283/2125; 64; 64/60; 692/4028/67/1059/2325; A549 Cells; Animals; Antibodies; Antigens; Antigens, CD19 - metabolism; Cancer therapies; Cell Line, Tumor; Cells; Cytokines; Cytotoxicity, Immunologic; FDA approval; Hematology; Humanities and Social Sciences; Humans; Immunotherapy; K562 Cells; Leukemia; Lymphocytes; Lymphoma; Medical schools; Medicine; Mice; multidisciplinary; Pediatrics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy; Science; Single-Chain Antibodies - genetics; Single-Chain Antibodies - metabolism; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Tumors; Xenograft Model Antitumor Assays
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep27130

T cells expressing chimeric antigen receptors (CARs) or the infusion of bispecific T-cell engagers (BITEs) have shown antitumor activity in humans for CD19-positive malignancies. While BITEs redirect the large reservoir of resident T cells to tumors, CAR T cells rely on significant in vivo expansion to exert antitumor activity. We have shown that it is feasible to modify T cells to secrete solid tumor antigen-specific BITEs, enabling T cells to redirect resident T cells to tumor cells. To adapt this approach to CD19-positive malignancies we now generated T cells expressing secretable, CD19-specific BITEs (CD19-ENG T cells). CD19-ENG T cells recognized tumor cells in an antigen-dependent manner as judged by cytokine production and tumor killing and redirected bystander T cells to tumor cells. Infusion of CD19-ENG T cells resulted in regression of leukemia or lymphoma in xenograft models and a survival advantage in comparison to control mice. Genetically modified T cells expressing engager molecules may present a promising addition to current CD19-targeted immunotherapies.