Contribution of host immunity to cyclophosphamide therapy of a chemically‐induced murine sarcoma

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Abstract
The contribution of host immune factors to the therapeutic effect of cyclophosphamide (CPA) on an antigenic chemically‐induced sarcoma (MCA‐2) transplanted in syngeneic mice with different immunological reactivity was investigated. In non‐sensitized mice, CPA failed to prevent survival of nascent tumour emboli comprising 105 cells. By contrast, the enhanced therapeutic efficiency of CPA against clinically detectable neoplasms or nascent tumours developing progressively from small inocula (104 cells) suggested that host sensitization may play a role in cyclophosphamide‐mediated regression of this tumour. The hypothesis was investigated by comparison of the effect of CPA treatment on palpable neoplasms growing in immunodepressed mice following wholebody irradiation (400 R) and specifically immunostimulated mice which had received irradiated (15,000 R) MCA‐2 cells, with their untreated immunocompetent counterparts. In the first group, the antitumour effect of CPA was noticeably weaker compared with that observed in normal mice, while in the second, the effect was markedly potentiated, so that palpable nodules comprising in excess of 5 × 106 cells underwent complete regression. Since the maximum level of resistance evoked by sarcoma MCA‐2 per se was of the order of 2 × 105 cells, the results indicate that pre‐immunization significantly augments the antitumour activity of CPA in this system. The specificity of the reaction was demonstrated by the failure of CPA to mediate complete regression of sarcoma MCA‐2 growing in mice previously immunized with normal muscle or an antigenically unrelated neoplasm (MCA‐7). Possible mechanisms for the synergistic activity of CPA and host immune factors in this tumour‐host system are discussed.
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