Premium
Combination therapy with thymosin α 1 potentiates the anti‐tumor activity of interleukin‐2 with cyclophosphamide in the treatment of the lewis lung carcinoma in mice
Author(s) -
Mastino Antonio,
Favalli Cartesio,
Grelli Sandro,
Rasi Guido,
Pica Francesca,
Goldstein Allan L.,
Garaci Enrico
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910500327
Subject(s) - lewis lung carcinoma , cyclophosphamide , immunotherapy , cytotoxic t cell , cd8 , tumor necrosis factor alpha , cytotoxicity , cancer research , thymosin , medicine , in vivo , immunology , spleen , interleukin 2 , tumor infiltrating lymphocytes , immune system , chemotherapy , in vitro , biology , cancer , metastasis , microbiology and biotechnology , biochemistry
In this study we have investigated the effects of thymosin α 1 (Tα 1 ) and interleukin‐2 (IL‐2), singly or in combination with cyclophosphamide (CY), on tumor growth, survival and cytotoxicity in C57BI/6NCrlBR mice with Lewis lung carcinoma (3LL). Combined administration of Tα 1 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 CDS) or NK‐cell (anti‐asialo GMI) 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 Tα 1 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.