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Macrophage-mediated destruction of human malignant cells in vivo
Abstract:
Macrophages require a plasma component, designated "recognition factor" (RF), for the expression of optimal function. The RF activity was profoundly depleted in plasma from patients with malignant disease, and the degree of depletion and the severity of the malignant state seemed to be related. Since experiments demonstrated that an active RF significantly inhibited tumor growth, clinical studies were initiated to investigate the influence of intratumor administration of an active RF fraction. Glucan, a potent macrophage activator, was also employed alone or combined with RF. These studies were undertaken to enhance the recognition of malignant cells by macrophages and to mobilize and activate macrophages intralesionally. The initial 9 patients studied had malignant melanoma, adenosquamous carcinoma of the lung, or carcinoma of the breast. Control and experimental lesions were injected; subsequently biopsies were performed at varying intervals for histologic evaluation. Always when glucan or glucan and RF fraction were administered intralesionally, the size of the lesion was strikingly reduced in as short a period as 5 days. This reduction was associated with necrosis of the tumor and a monocytic infiltrate. In small lesions, resolution was complete, whereas in large lesions, resolution was partial. The amount of glucan injected and the quantity of residual tumor appeared to be related. The induced necrosis of the tumor nodule was associated with an increase in plasma levels of circulating RF activity.
Insights
This study found that administering a recognition factor (RF) fraction and glucan into tumors significantly reduced lesion size in cancer patients. This treatment enhanced macrophage activity, leading to tumor necrosis and improved outcomes.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Macrophages require a plasma component, recognition factor (RF), for optimal function.
- RF activity is depleted in cancer patients' plasma, correlating with disease severity.
- Active RF inhibits tumor growth, suggesting therapeutic potential.
Purpose of the Study:
- To investigate the influence of intratumor administration of an active RF fraction.
- To evaluate the combination of RF with glucan, a macrophage activator, for cancer therapy.
- To enhance malignant cell recognition by macrophages and activate them intralesionally.
Main Methods:
- Intratumor injections of RF fraction and/or glucan in 9 patients with malignant melanoma, lung, or breast cancer.
- Histologic evaluation of biopsies at varying intervals post-injection.
- Monitoring of lesion size reduction and associated cellular changes.
Main Results:
- Intralesional glucan or glucan and RF fraction administration led to striking lesion size reduction within 5 days.
- Treatment induced tumor necrosis and a monocytic infiltrate.
- Complete resolution occurred in small lesions; partial resolution in larger ones.
Conclusions:
- Intratumor RF and glucan therapy shows promise in reducing tumor size and inducing necrosis.
- The treatment enhances macrophage-mediated anti-tumor responses.
- Increased plasma RF activity was observed following tumor necrosis induction.