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Tumor‐cell lysis by in‐situ ‐activated human peripheral‐blood mononuclear cells
Author(s) -
Smans Karine A.,
Hoylaerts Marc F.,
Hendrickx Herman F.,
Goergen Martine J.,
De Broe Marc E.
Publication year - 1991
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/ijc.2910470321
Subject(s) - peripheral blood mononuclear cell , antibody dependent cell mediated cytotoxicity , lysis , microbiology and biotechnology , monoclonal antibody , cytotoxicity , chemistry , antibody , biology , in vitro , immunology , biochemistry
A heteroconjugate (HC) was synthesized between OKT3 and monoclonal antibody (MAb) 7E8, which specifically reacts with the tumor marker placental alkaline phosphatase (PLAP). Similarly to OKT3, in vitro , the HC induced a dose‐dependent proliferation response of human peripheral‐blood mononuclear cells (PBMCs) and, in concert with rlL‐2, it progressively activated T cells over a 4‐day period. In co‐cultures of continuously activated PBMCs and M0 4 tumor cells (non‐MHC‐restricted mouse fibroblasts transfected with the cDNA for PLAP), the HC (25 ng/ml), again acting in concert with rlL‐2, induced specific lysis of the MO 4 cells. This process occurred progressively over 2 to 3 days and was monitored from the release in the supernatant fluid of cellular 3 H‐L‐leucine, but also from analyses involving the remaining non‐lysed cancer cells, i.e. , by estimates of their protein content, by measurements of their viability, and most accurately by determinations of their PLAP content. Antibody 7E8 by itself induced a weak tumor‐cell lysis (ADCC), potentiated by the addition of rlL‐2. However, after 7 days of PBMC‐preactivation with the HC and rlL‐2, antibody 7E8 no longer mediated any ADCC, whereas the HC‐dependent lysis was further potentiated. The observed proliferation of T cells and development of cytotoxicity at low concentrations of HC and rlL‐2 support the idea that a moderate but continuous T‐cell activation combined with T‐cell targeting is sufficient for the induction of progressive and efficient tumor‐cell lysis.