Requirements for the construction of antibody heterodimers for the direction of lysis of tumors by human T cells.
We constructed a series of MAb heterodimers consisting of the J5 (anti-common acute lymphoblastic leukemia antigen [CALLA]) antibody and antibodies to a variety of structures present on the surface of activated human T cells, including CD3 antigen (T cell receptor-associated glycoproteins), CD2 antigen (T11/E-rosette receptor), CD25 antigen (IL-2 receptor), and the transferrin receptor. We tested the ability of these heterodimers to direct a CD2 + CD3 + CD8 + CD4 - CD25 + transferrin receptor + MHC-restricted human cytolytic T lymphocyte (CTL) clone to lyse a CALLA + human tumor in vitro. Only heterodimers containing an anti-CD3 antibody or activating antibodies to CD2 could direct the clone to lyse these human tumor targets, even when the clone was additionally activated with anti-CD3 or anti-CD2 antibodies. Our findings may have implications in the design of strategies for the use of such reagents in the treatment of human neoplasia.
Scott
C F
CF
Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Blättler
W A
WA
Lambert
J M
JM
Kalish
R S
RS
Morimoto
C
C
Schlossman
S F
SF
D000906:Antibodies / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D002051:Burkitt Lymphoma; D002461:Cell Line, Transformed; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D015260:Neprilysin; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011990:Receptors, Transferrin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology*
D000906:Antibodies; D000912:Antibodies, Neoplasm; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D011948:Receptors, Antigen, T-Cell; D011990:Receptors, Transferrin; D015260:Neprilysin