Combination therapy with thymosin alpha 1 potentiates the anti-tumor activity of interleukin-2 with cyclophosphamide in the treatment of the Lewis lung carcinoma in mice.
Mastino. A A; Favalli. C C; Grelli. S S; Rasi. G G; Pica. F F; Goldstein. A L AL; Garaci. E E
Key Findings
- Thymosin‑alpha‑1 boosts the anti‑tumor effect of IL‑2 when combined with cyclophosphamide in mice
- The triple combo caused full tumor regression and long‑term survival in the tested mice
- The benefit depends on intact T‑cells and NK cells; removing them cancels the effect
Practical Outcomes
- The results are not ready for self‑experimentation or off‑label use; they show a promising pre‑clinical cancer strategy that requires clinical testing and medical supervision before any real‑world application.
Summary
In a mouse study, giving thymosin‑alpha‑1 together with interleukin‑2 and a chemotherapy drug (cyclophosphamide) completely eliminated lung tumors, but the effect disappeared when immune cells were removed. This is an early‑stage cancer experiment in animals, not a human protocol.
Abstract
In this study we have investigated the effects of thymosin alpha 1 (T alpha 1) 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 T alpha 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 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 T alpha 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.
Study Information
pubmed
1992
1992-02-01T00:00:00.000Z
10.1002/ijc.2910500327
52
29