ABSTRACT
An approach, first studied in detail in a variety of murine model systems, is the exploration of the specific immunomodulatory properties of cyclophosphamide (CY), followed by treatment with interleukin-2 (IL-2). Since in other experimental systems synergism between subcytotoxic doses of chemotherapeutic agents with cytokines have been demonstrated, it cannot be ruled out that the demonstrated synergism between noncytotoxic doses of CY and cytokines in vivo could also be explained by a direct subcytotoxic effect of the chemotherapeutic agent and its metabolites on the tumor cell itself. The broad spectrum of immunomodulatory properties of CY has led to the exploration of combinations of CY and IL-2. Precursors of T suppressor cells are especially sensitive to the effects of low-dose CY followed by mature B cells and then T helper cells, while cytotoxic precursor cells and cytotoxic effector cells appear to be most resistant to CY administration.
