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CD3xCD19 bispecific antibodies and CD28 bivalent antibodies enhance T‐cell reactivity against autologous leukemic cells in pediatric B‐ALL bone marrow
Author(s) -
Manzke Oliver,
Berthold Frank,
Huebel Kai,
Tesch Hans,
Diehl Volker,
Bohlen Heribert
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990301)80:5<715::aid-ijc15>3.0.co;2-p
Subject(s) - cd28 , t cell , bone marrow , cytotoxic t cell , antibody , immunology , elispot , cd8 , cd3 , immunophenotyping , b cell , medicine , microbiology and biotechnology , cancer research , flow cytometry , biology , antigen , immune system , in vitro , biochemistry
Bispecific CD3xCD19 antibodies and CD28 co‐stimulating antibodies were used to activate T cells in bone marrow aspirates (n = 8) of children with B cell–derived acute lymphoblastic leukemia. Bone marrow specimens were incubated for 10 days with CD3xCD19 bispecific and CD28 antibodies. Changes in the numbers of T lymphocytes and tumoral B cells as well as surface expression of T cell–activation markers were determined by flow cytometry, and cytokines (human IFN‐γ, IL‐2, IL‐4 and IL‐12) were measured in the cell culture supernatant. In 7 of 8 bone marrow samples, an increase in the number of CD4‐ and CD8‐positive T lymphocytes was found, which correlated with an up‐regulation of T cell–activation markers. Additionally, we demonstrated a decrease of tumoral B cells in 3 samples and enhanced cytotoxic T‐cell activity against autologous malignant B cells. ELISpot analyses in an autologous Epstein‐Barr virus model showed that bispecific antibodies (CD3xCD19+CD28) were more potent at generating T‐cell responses against autologous and allogeneic tumoral targets than a combination of monospecific antibodies (CD3+CD28). Thus, T‐cell targeting by CD3xCD19 bispecific and CD28 antibodies may be used to eliminate leukemic B cells ex vivo and reconstitute immunological control of residual malignant disease by the induction of anti‐tumoral T‐cell responses. Int. J. Cancer 80:715–722, 1999. © 1999 Wiley‐Liss, Inc.