Antibody-mediated B-cell depletion before adoptive immunotherapy with T cells expressing CD20-specific chimeric T-cell receptors facilitates eradication of leukemia in immunocompetent mice.

Publication Type:

Journal Article

Source:

Blood, Volume 114, Issue 27, p.5454-63 (2009)

Keywords:

2009, Animals, Antibodies, Monoclonal, Antigens, CD20, Antigens, CD3, B-Lymphocytes, Cell Line, Tumor, Cell Processing Core Facility, Cell Survival, Center-Authored Paper, Clinical Research Division, Comparative Medicine Core Facility, Cytokine Analysis Core Facility, Flow Cytometry Core Facility, Genomics Core Facility, Humans, Immune Monitoring Core Facility, Immunotherapy, Adoptive, LEUKEMIA, MICE, Mice, Inbred BALB C, Mice, Transgenic, Receptors, Antigen, T-Cell, Shared Resources, Specimen Processing Core Facility, Survival Analysis, T-Lymphocytes

Abstract:

We have established a model of leukemia immunotherapy using T cells expressing chimeric T-cell receptors (cTCRs) targeting the CD20 molecule expressed on normal and neoplastic B cells. After transfer into human CD20 (hCD20) transgenic mice, cTCR(+) T cells showed antigen-specific delayed egress from the lungs, concomitant with T-cell deletion. Few cTCR(+) T cells reached the bone marrow (BM) in hCD20 transgenic mice, precluding effectiveness against leukemia. Anti-hCD20 antibody-mediated B-cell depletion before adoptive T-cell therapy permitted egress of mouse CD20-specific cTCR(+) T cells from the lungs, enhanced T-cell survival, and promoted cTCR(+) T cell-dependent elimination of established mouse CD20(+) leukemia. Furthermore, CD20-specific cTCR(+) T cells eliminated residual B cells refractory to depletion with monoclonal antibodies. These findings suggest that combination of antibody therapy that depletes antigen-expressing normal tissues with adoptive T-cell immunotherapy enhances the ability of cTCR(+) T cells to survive and control tumors.