Year: 2017
Type: article
Abstract: Many patients with B-cell malignancies can be successfully treated, although tumor eradication is rarely achieved. T-cell-directed killing of tumor cells using engineered T-cells or bispecific antibodies is a promising approach for the treatment of hematologic malignancies.We investigated the efficacy of CD19xCD3 DART bispecific antibody in a broad panel of human primary B-cell malignancies. The CD19xCD3 DART identified 2 distinct subsets of patients, in which the neoplastic lymphocytes were eliminated with rapid or slow kinetics. Delayed responses were always overcome by a prolonged or repeated DART exposure. Both CD4 and CD8 effector cytotoxic cells were generated, and DART-mediated killing of CD4+ cells into cytotoxic effectors required the presence of CD8+ cells. Serial exposures to DART led to the exponential expansion of CD4+ and CD8+ cells and to the sequential ablation of neoplastic cells in absence of a PD-L1-mediated exhaustion. Lastly, patient-derived neoplastic B-cells (B-Acute Lymphoblast Leukemia and Diffuse Large B Cell Lymphoma) could be proficiently eradicated in a xenograft mouse model by DART-armed cytokine induced killer (CIK) cells.Collectively, patient tailored DART exposures can result in the effective elimination of CD19 positive leukemia and B-cell lymphoma and the association of bispecific antibodies with unmatched CIK cells represents an effective modality for the treatment of CD19 positive leukemia/lymphoma.
Source: OncoImmunology
Authors: Paola Circosta, Angela Rita Elia, Indira Landra, Rodolfo Machiorlatti, Maria Todaro, Sabrina Aliberti, Davide Brusa, Silvia Deaglio, Sabina Chiaretti, Riccardo Bruna, Daniela Gottardi, Massimo Massaia, Filomena Di Giacomo, Anna Rita Guarini, Robin Foà, Peter W. Kyriakides, Rohan Bareja, Olivier Elemento, Gurunadh R. Chichili, Emanuele Monteleone, Paul A. Moore, Syd Johnson, Ezio Bonvini, Alessandro Cignetti, Giorgio Inghirami
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,913
OpenAlex ID: W2727279249