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Therapeutical effect of activated human macrophages on a human tumor line growing in nude mice
S Ben-Efraim1, C Tak, J C Romijn
1Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Israel.
Abstract:
Human peritoneal macrophages were collected from dialysis bags of renal patients on Continuous Ambulatory Peritoneal Dialysis (CAPD), during an inflammation-free period. The macrophage suspension was cultured in presence of bacterial lipopolysaccharide (LPS) and phorbol myristate acetate (TPA). The cultured macrophages were tested for therapeutic effectiveness against a human tumor-cell line, RC43, implanted subcutaneously in NMRI nude mice. The macrophages were injected around the tumor starting from the 14th day after inoculation, when the tumor growth was already detectable (mean tumor size 7 mm). Three injections of macrophages on days 14, 18 and 21 induced hemorrhagic patches at the tumor site and almost complete regression of the tumor. One injection of macrophages cultured either in presence of LPS+TPA or of LPS+TPA+PGE2 resulted in marked slow-down of the tumor growth. Injection of either TNF-alpha (4000 U/mouse) or PGE2 (150 ng/mouse) given at the site of the palpable small tumor had no effect. Macrophages cultured in medium or in medium supplied with either TPA, LPS or TPA+LPS, were not effective in nude mice bearing large (16 to 19 mm) tumors. The results obtained suggest that activated human macrophages might be therapeutically effective at certain stages of human cancer.
Insights
Activated human macrophages show therapeutic potential against cancer. Macrophages cultured with specific agents and injected into tumors led to significant tumor regression in mice, suggesting a promising cancer treatment strategy.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Human peritoneal macrophages from Continuous Ambulatory Peritoneal Dialysis (CAPD) patients were utilized.
- Macrophages were cultured with bacterial lipopolysaccharide (LPS) and phorbol myristate acetate (TPA) to activate them.
Purpose of the Study:
- To evaluate the therapeutic effectiveness of activated human macrophages against a human tumor cell line (RC43) in vivo.
- To determine the impact of macrophage activation methods on anti-tumor efficacy.
Main Methods:
- Human peritoneal macrophages were cultured with LPS and TPA.
- Activated macrophages were injected into subcutaneous RC43 tumors in NMRI nude mice starting on day 14 post-inoculation.
- Tumor growth and regression were monitored after macrophage injections.
Main Results:
- Three injections of activated macrophages induced hemorrhagic patches and near-complete tumor regression.
- A single injection of LPS+TPA or LPS+TPA+PGE2 cultured macrophages significantly slowed tumor growth.
- Unactivated macrophages or TNF-alpha/PGE2 alone had no significant effect on tumor regression, especially in larger tumors.
Conclusions:
- Activated human macrophages demonstrate significant anti-tumor activity in a murine model.
- The timing and method of macrophage activation influence therapeutic effectiveness.
- These findings suggest a potential role for activated macrophages in cancer therapy, particularly in earlier stages of tumor development.