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Antitumor effect of Lentinan on syngeneic and autologous tumor-host systems, and suppression on chemical carcinogenesis
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yeast glucan, C. Parvum, BCG, PI:C and so on. First of all Lentinan is a fully purified neutral polysaccharide (PS) and its chemical structure is strictly characterized. Lentinan does not enhance phagocytic activity of RES' and not activate M~ for tumoricidal activity in vitro, thus it can be distinguished from many other RES stimulants. Lentinan induced peritoneal M~ exerted prominently depressed prostaglandin release, while C. parvum, BCG, PI:C, zymosan and yeast glucan cause the inverse effects, which might be the shortness of these potentiators, for PGs released from M# certainly cause negative impact on cellular and humoral immune responses displaying critical roles for host defenses against cancer. Lentinan restores and/or stimulates anti TATA delayed hyperreaction (DHR). This tumor antigen directed DHR and tumor growth inhibition against syngeneic tumor revealed to be well correlated. Lentinan does not activate natural killer cells both in vivo and in vitro at optimum doses for its antitumor action and this can be explained by the absence of any significant degree of interferon induction from M~ in vivo and in vitro. This Lentinan behaviors are also distinct from other polyanions, BCG and C. parvum. Nonetheless of these distinct impact on M~ functions, Lentinan does activate M~ for tumoricidal activity when administered systematically in vivo. The observed in vivo activation of M~ by Lentinan might be explained by the indirect action of C3b, for Lentinan efficiently activates APC, or by the activation of M~ by increasingly produced lymphokines from Lytl+2-3 - cells stimulated by Lentinan. Lentinan does augment the susceptibility of Lytl+2+3 + T cells to helper factor(s) resulting in the augmented T-T cooperation in killer T cells induction and resulting in the augmented antibody production against T dependent antigen. In conclusion, Lentinan augments T-T interaction and T-B interaction probably by stimulating accessory cell function and by production of efficient amount of helper factors which also augment tumor antigen directed delayed type hyperreaction as expressed by antibody dependent M# mediated cytotoxicity.
LENTINAN INDUCED AUGMENTED KILLER T CELL GENERATION FROM THYMOCYTES IS DUE TO THE ELEVATED SUSCEPTIBILITY TO HELPER FACTOR(S). J. Hamuro. M. Takarada, N. Kashima, K. Mitsu@i Central Research Laboratories, Ajinomoto Co., Inc., Yokohama, Japan. Immune potentiatingand/or restorating action of T cell specific immune adjuvant, Lentinan, have been partially explained by its i ~ u n o l o g i c a l activity to augment pfc induction against T dependent antigen, and allo re~ctiv~ and H-2 restricted hapten specific killer T cell generation. Thymocytes mainly composed of Lytl+2+3 + cells are generally inert in allo-reactive and H-2 restricted hapten specific killer T cell inducting responses, however efficient induction of killer T cells was observed when MLR cultures were set up in the presence of helper T cell factor(s) produced by polyclonal activation of splenocytes by ConA. Thymocytes harvested after ip injection of Lentinan at 0.001-0.i mg/kg exerted an elevated incorporation of 3HTdR in the presence of ConA while no elevation was observed in the absence. Thymocytes harvested after ip Lentinan injection generated neither alloreactive nor H-2 restricted hapten specific killer T cells, but in the presence of helper factor(s) generated i0 times higher degree of killer T cell activity than thymocytes from non-treated. Therefore Lentinan might elevate the susceptibility of Lytl+2+3 + cells to helper factor(s) triggering the differentiation of Lytl+2+3 + thymocytes into Lytl + and Lyt2+3 + cells. The mechanisms underlying in the elevation of thymocytes reactivity in killer T cell generation is still unclear but Lentinan treated thymocytes produced no killer T cell activity in the absence of helper T cell factor(s). In syngeneic tumor bearing murine systems, such as C3H/He-X5563, C57BL/6-EL4, splenocytes and thymocytes generated depressed killer T cells, however the thymocytes itself generated killer T cells to some degrees in the absence of helper factor(s). Furthermore thymocytes bacame more sensitive to helper factors at the later stage of tumor growth in C57BL/6-EL4 systems. In this context Lentinan would present a useful tool to improve the depressed immune reactivity of syngeneic tumor bearing hosts. The new finding herein described would contribute to the development of new T cell specific cancer immunotherapy as a distinct immunopharmacological drug.
42
yeast glucan, C. Parvum, BCG, PI:C and so on. First of all Lentinan is a fully purified neutral polysaccharide (PS) and its chemical structure is strictly characterized. Lentinan does not enhance phagocytic activity of RES' and not activate M~ for tumoricidal activity in vitro, thus it can be distinguished from many other RES stimulants. Lentinan induced peritoneal M~ exerted prominently depressed prostaglandin release, while C. parvum, BCG, PI:C, zymosan and yeast glucan cause the inverse effects, which might be the shortness of these potentiators, for PGs released from M# certainly cause negative impact on cellular and humoral immune responses displaying critical roles for host defenses against cancer. Lentinan restores and/or stimulates anti TATA delayed hyperreaction (DHR). This tumor antigen directed DHR and tumor growth inhibition against syngeneic tumor revealed to be well correlated. Lentinan does not activate natural killer cells both in vivo and in vitro at optimum doses for its antitumor action and this can be explained by the absence of any significant degree of interferon induction from M~ in vivo and in vitro. This Lentinan behaviors are also distinct from other polyanions, BCG and C. parvum. Nonetheless of these distinct impact on M~ functions, Lentinan does activate M~ for tumoricidal activity when administered systematically in vivo. The observed in vivo activation of M~ by Lentinan might be explained by the indirect action of C3b, for Lentinan efficiently activates APC, or by the activation of M~ by increasingly produced lymphokines from Lytl+2-3 - cells stimulated by Lentinan. Lentinan does augment the susceptibility of Lytl+2+3 + T cells to helper factor(s) resulting in the augmented T-T cooperation in killer T cells induction and resulting in the augmented antibody production against T dependent antigen. In conclusion, Lentinan augments T-T interaction and T-B interaction probably by stimulating accessory cell function and by production of efficient amount of helper factors which also augment tumor antigen directed delayed type hyperreaction as expressed by antibody dependent M# mediated cytotoxicity.
LENTINAN INDUCED AUGMENTED KILLER T CELL GENERATION FROM THYMOCYTES IS DUE TO THE ELEVATED SUSCEPTIBILITY TO HELPER FACTOR(S). J. Hamuro. M. Takarada, N. Kashima, K. Mitsu@i Central Research Laboratories, Ajinomoto Co., Inc., Yokohama, Japan. Immune potentiatingand/or restorating action of T cell specific immune adjuvant, Lentinan, have been partially explained by its i ~ u n o l o g i c a l activity to augment pfc induction against T dependent antigen, and allo re~ctiv~ and H-2 restricted hapten specific killer T cell generation. Thymocytes mainly composed of Lytl+2+3 + cells are generally inert in allo-reactive and H-2 restricted hapten specific killer T cell inducting responses, however efficient induction of killer T cells was observed when MLR cultures were set up in the presence of helper T cell factor(s) produced by polyclonal activation of splenocytes by ConA. Thymocytes harvested after ip injection of Lentinan at 0.001-0.i mg/kg exerted an elevated incorporation of 3HTdR in the presence of ConA while no elevation was observed in the absence. Thymocytes harvested after ip Lentinan injection generated neither alloreactive nor H-2 restricted hapten specific killer T cells, but in the presence of helper factor(s) generated i0 times higher degree of killer T cell activity than thymocytes from non-treated. Therefore Lentinan might elevate the susceptibility of Lytl+2+3 + cells to helper factor(s) triggering the differentiation of Lytl+2+3 + thymocytes into Lytl + and Lyt2+3 + cells. The mechanisms underlying in the elevation of thymocytes reactivity in killer T cell generation is still unclear but Lentinan treated thymocytes produced no killer T cell activity in the absence of helper T cell factor(s). In syngeneic tumor bearing murine systems, such as C3H/He-X5563, C57BL/6-EL4, splenocytes and thymocytes generated depressed killer T cells, however the thymocytes itself generated killer T cells to some degrees in the absence of helper factor(s). Furthermore thymocytes bacame more sensitive to helper factors at the later stage of tumor growth in C57BL/6-EL4 systems. In this context Lentinan would present a useful tool to improve the depressed immune reactivity of syngeneic tumor bearing hosts. The new finding herein described would contribute to the development of new T cell specific cancer immunotherapy as a distinct immunopharmacological drug.
42