A Novel Bispecific T-Cell Engager (CD1a x CD3ε) BTCE Is Effective against Cortical-Derived T Cell Acute Lymphoblastic Leukemia (T-ALL) Cells

Cancers

Andrea Ballerini¹  Maria Teresa Di Martino²  Katia Grillone²  Caterina Riillo²  Mariangela Lopreiato²  Maria Anna Siciliano²  Daniele Caracciolo²  Giada Juli²  Nicoletta Polerಠ Marco Rossi²  Serena Ascrizzi²  Pierfrancesco Tassone²  Pierosandro Tagliaferri²  Domenico Britti³  Giovanni Loprete³  Licia Pensabene⁴  Simona Sestito⁴  Massimo Gentile⁵  Gabriella Talarico⁶  Mariamena Arbitrio⁷  Francesca Scionti⁸  Franca Maria Tuccillo⁹  Patrizia Bonelli⁹  Eulalia Galea^1,10  Maria Concetta Galati^1,10 

[1] BiovelocITA srl, 20122 Milan, Italy;Department of Experimental and Clinical Medicine, Magna Græcia University, 88100 Catanzaro, Italy;Department of Health Sciences, Magna Graecia University, 88100 Catanzaro, Italy;Department of Medical and Surgical Sciences, Magna Græcia University, 88100 Catanzaro, Italy;Hematology Unit, Annunziata Hospital, 87100 Cosenza, Italy;Immunotransfusion Service Unit, Pugliese-Ciaccio Hospital, 88100 Catanzaro, Italy;Institute of Research and Biomedical Innovation (IRIB), Italian National Council (CNR), 88100 Catanzaro, Italy;Institute of Research and Biomedical Innovation (IRIB), Italian National Council (CNR), 98164 Messina, Italy;Istituto Nazionale Tumori IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy;Pediatric Hemato-Oncology Unit, Pugliese-Ciaccio Hospital, 88100 Catanzaro, Italy;

关键词: T-ALL;    acute lymphoblastic leukemia;    ALL;    CD1a;    bispecific T cell engager;    BTCE;   

DOI  :  10.3390/cancers14122886

来源: DOAJ

【 摘 要 】

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. To this end, we generated a novel asymmetric (2 + 1) bispecific T-cell engager (BTCE) targeting CD1a and CD3ε (CD1a x CD3ε) starting from the development of a novel mAb named UMG2. UMG2 mAb reacts against CD1a, a glycoprotein highly expressed by cortical T-ALL cells. Importantly, no UMG2 binding was found on normal T-cells. CD1a x CD3ε induced high T-cell mediated cytotoxicity against CD1a+ T-ALL cells in vitro, as demonstrated by the concentration-dependent increase of T-cell proliferation, degranulation, induction of cell surface activation markers, and secretion of pro-inflammatory cytokines. Most importantly, in a PBMC-reconstituted NGS mouse model bearing human T-ALL, CD1a x CD3ε significantly inhibited the growth of human T-ALL xenografts, translating into a significant survival advantage of treated animals. In conclusion, CD1a x CD3ε is a novel BTCE highly active against CD1a-expressing cortical-derived T-ALL cells suitable for clinical development as an effective therapeutic option for this rare and aggressive disease.

【 授权许可】

Unknown