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.
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.
James
Scott E
SE
Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Orgun
Nural N
NN
Tedder
Thomas F
TF
Shlomchik
Mark J
MJ
Jensen
Michael C
MC
Lin
Yukang
Y
Greenberg
Philip D
PD
Press
Oliver W
OW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D018951:Antigens, CD20 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016219:Immunotherapy, Adoptive; D007938:Leukemia / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D011948:Receptors, Antigen, T-Cell