Tumor‐cell lysis by in‐situ‐activated human peripheral‐blood mononuclear cells

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Abstract
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 M04 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 MO4 cells. This process occurred progressively over 2 to 3 days and was monitored from the release in the supernatant fluid of cellular 3H‐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.

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