TY - JOUR
T1 - Combination therapy with thymosin α1 potentiates the anti-tumor activity of interleukin-2 with cyclophosphamide in the treatment of the Lewis lung carcinoma in mice
AU - Mastino, A.
AU - Favalli, C.
AU - Grelli, S.
AU - Rasi, G.
AU - Pica, F.
AU - Goldstein, A. L.
AU - Garaci, E.
PY - 1992
Y1 - 1992
N2 - In this study we have investigated the effects of thymosin α1 (Tα1) and interleukin-2 (IL-2), singly or in combination with cyclophosphamide (CY), on tumor growth, survival and cytotoxicity in C57Bl/6NCrlBR mice with Lewis lung carcinoma (3LL). Combined administration of Tα1 plus IL-2, after CY treatment, was much more effective than use of each biological response modifier (BRM) alone, and induced complete tumor regression in all of the mice studied. Combination immunotherapy alone without CY only slightly reduced the rate of tumor growth, and these results are in accordance with previous studied which showed that the 3LL carcinoma is resistant to cytokines. Combined chemo-immunotherapy also increased the cytotoxicity of spleen cells and markedly enhanced long-term survival in all treated animals. Depletion of immune cells, using either total-body sub-lethal irradiation (400 rads) or antibodies directed against T-cell (anti-CD4 and CD8) or NK-cell (anti-asialo GM1) populations, abolished the positive response to combination therapy. Histological analysis of the tumors obtained from mice treated with combination chemo-immunotherapy revealed a high number of infiltrating lymphoid cells surrounding a well-circumscribed area of necrosis consisting solely of dead cells. Our studies show that Tα1 potentiates IL-2-induced cytotoxic activities in vitro as well in vivo, and that these compounds have a powerful anti-tumor action when associated with chemotherapy.
AB - In this study we have investigated the effects of thymosin α1 (Tα1) and interleukin-2 (IL-2), singly or in combination with cyclophosphamide (CY), on tumor growth, survival and cytotoxicity in C57Bl/6NCrlBR mice with Lewis lung carcinoma (3LL). Combined administration of Tα1 plus IL-2, after CY treatment, was much more effective than use of each biological response modifier (BRM) alone, and induced complete tumor regression in all of the mice studied. Combination immunotherapy alone without CY only slightly reduced the rate of tumor growth, and these results are in accordance with previous studied which showed that the 3LL carcinoma is resistant to cytokines. Combined chemo-immunotherapy also increased the cytotoxicity of spleen cells and markedly enhanced long-term survival in all treated animals. Depletion of immune cells, using either total-body sub-lethal irradiation (400 rads) or antibodies directed against T-cell (anti-CD4 and CD8) or NK-cell (anti-asialo GM1) populations, abolished the positive response to combination therapy. Histological analysis of the tumors obtained from mice treated with combination chemo-immunotherapy revealed a high number of infiltrating lymphoid cells surrounding a well-circumscribed area of necrosis consisting solely of dead cells. Our studies show that Tα1 potentiates IL-2-induced cytotoxic activities in vitro as well in vivo, and that these compounds have a powerful anti-tumor action when associated with chemotherapy.
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M3 - Article
C2 - 1735618
AN - SCOPUS:0026586234
VL - 50
SP - 493
EP - 499
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 3
ER -