Tumor-cell lysis by in-situ-activated human peripheral-blood mononuclear cells.
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 rIL-2, it progressively activated T cells over a 4-day period. In co-cultures of continuously activated PBMCs and MO4 tumor cells (non-MHC-restricted mouse fibroblasts transfected with the cDNA for PLAP), the HC (25 ng/ml), again acting in concert with rIL-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 rIL-2. However, after 7 days of PBMC-preactivation with the HC and rIL-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 rIL-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.
Smans
K A
KA
Department of Nephrology-Hypertension, University of Antwerp, Belgium.
Hoylaerts
M F
MF
Hendrickx
H F
HF
Goergen
M J
MJ
De Broe
M E
ME
D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D010920:Placenta / Q000201:enzymology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007376:Interleukin-2; D000469:Alkaline Phosphatase