Trial of anticancer immunotherapy with immobilized pokeweed mitogen: Immunotherapy by extracorporeal circulation

Abstract

For the purpose of activating the immune system in the living body, we made use of pokeweed mitogen (PWM). PWM, a type of lectin, has the potential to induce anticancer cells. In order to utilize this potential and apply it to cancer therapy by hemoperfusion with PWM, the lectin is immobilized on the surface of synthetic polymer beads and these beads are packed into a minicolumn. Human peripheral lymphocytes were activated by circulatory contact stimulation through the PWM column for 1h. After circulatory contact stimulation through the column, lymphocytes were collected and used as effector cells. Cytotoxicity tests were measured by 51Cr-release assay using K-562 cells and Daudi cells for targets. This material could enhance natural killer activity and induce cytotoxicity against natural-killer-resistant Daudi cells. Lymphocytes activated by the PWM column were injected intraregionally into nude mice bearing MKN-1 tumor, and suppression of tumor growth was recognized. Anticancer activities by direct hemoperfusion treatment with a PWM minicolumn were examined in Vx2-tumor-bearing rabbits. A single treatment using the PWM column was performed 6 days after tumor inoculation. Suppression of the tumor growth was observable for 25 days. PWM minicolumns are a likely anticancer material, acting as immunomodulators.

Induction of antitumor activities in spleen cells from mice and rats activated with lipopolysaccharide immobilized on beads

“…It was reported that immobilized pokeweed mitogen induced cytolytic activity immediately after stimulation [12]. These results suggested that effector cells stimulated with immobilized pokeweed mitogen obtained their cytotoxicity directly; on the other hand, those stimulated with immobilized LPS produced humoral factors and changed the killer cells indirectly.…”

“…In order to resolve these problems, an extracorporeal circulatory system with immunostimulants can be used for immunotherapy. Greaves and Bauminger [4] reported that phytohemagglutinin bound to Sepharose beads could activate lymphocytes, and that antitumor activity could be induced by extracorporeal circulation with immobilized interferon [7] or immobilized pokeweed mitogen [12].…”

Plant Lectins as Inhibitors of Tumour Growth and Modulators of Host Immune Response

“…Hajto et al [8] have thrown light on the action of lectins on cellular and cytokine responses in vivo and in vitro, and Vehmeyer et al [9] have demonstrated the occurrence of a (Tgalactoside-specific lectin in mouse tumour and that this endogenous lectin has pronounced immu nomodulatory capacity. Numa et al [10] have used lectin-activated peripheral blood mono nuclear cells for immunotherapy of human cancers.…”