Cancer patients are often treated with biological response modifiers to enhance immunological functions. However, little is known about the actual mechanism of action of many of these substances. Therefore, we were interested in the effect of i.p. treatment with porcine low-molecular-weight spleen peptides, which are used during supportive cancer therapy, on lymphoid cell populations and function in mice. After treatment with 0.5 microgram peptides/kg body weight for 14 consecutive days, lymphokine secretion and the generation of cytotoxic T-cells were significantly enhanced as compared with controls. However, there was no effect on the number of cells or the percentage of cells expressing functional surface markers in secondary lymphoid organs.
Preparations of splenic peptides under the name of Polyerga are being tested in numerous experimental immunomodulating and antitumorous models and are also used during supportive treatment of tumorous patients. Further, the incidence of experimental lung metastases of melanoma cells in mice was significantly reduced if we used Polyerga preparations. The aim of our investigation was to determine whether Polyerga is active directly against tumor cells or whether its activity is manifested by modulating immune and other possible abilities of the organism. To clarify the problem glycopeptides containing Polyerga were incubated with melanoma B16F10 cells in vitro and the plating efficiency of these cells determined when cultivated in medium, or in medium with different doses of the same Polyerga preparation. The cells preincubated in medium only reacted to the addition of increasing doses of Polyerga, 150 pg or more, by raising colonies number. However, 24-h incubation of melanoma cells in the presence of 150 micrograms of Polyerga per ml significantly reduced the number of tumor cell colonies in comparison to the corresponding cell cultures previously not exposed to Polyerga. These in vitro studies were extended to in vivo application using C57B1/GoZgr mice injected i.v. with melanoma cells pretreated with Polyerga in vitro or previously not treated. A group of the treated mice was further injected i.p. with Polyerga. All the mice were killed at a particular time and the number of lung nodules determined. A significant difference to the control values was noticed in each group that used Polyerga, regardless of the exposure of melanoma cells to Polyerga in vitro, in vivo or to combined treatment. The efficiency of Polyerga application 7 days following i.v. injection of control melanoma cells (cultivated in medium only) when the nodules already exist, was further evaluated in a combined treatment using DTIC, a drug of choice in melanomas. The smallest incidence of experimental lung metastases was observed in the group exposed to the combination of DTIC and Polyerga. Polyerga preparation is thus active against melanoma cells, particularly in vivo and if combined with chemotherapy.
Patients with inoperable head and neck cancer were treated with a spleen peptide preparation (Polyerga) in a phase III randomized, placebo-controlled double-blind study during chemotherapy (cisplatin/carboplatin, 5-fluorouracil) to investigate further the efficacy of this peptide preparation as supportive treatment under chemotherapy. Immunological changes as well as quality of life aspects were examined. Forty patients were included in this study. The peptide preparation had a significant stabilizing effect on the peripheral blood lymphocyte status during chemotherapy cycles (Student t-test, p = 0.05) and tended to stabilize the shift of granulocyte count (Student t-test, p = 0.18). In addition, the group receiving the verum showed a remarkable stabilization of body weight (Mann-Whitney U-test, p = 0.17) during chemotherapy treatment and the generally observed increase of fatigue-inertia during the chemotherapy cycles was significantly reduced (Student t-test, p = 0.01).
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