Because of the documented role of T lymphocytes in tumor rejection, studies are in progress to evaluate the biological and antitumor effects of recombinant human interleukin-7 (rhIL-7). The administration of rhIL-7 to mice induces a pronounced systemic leukocytosis consisting of mostly pre-B cells with a considerable increase also in CD8+ lymphocytes. Splenic T cells obtained from mice treated with rhIL-7 are able to generate an accelerated and enhanced response to mitogenic and allogeneic stimulation compared to T cells from control mice. Further, rhIL-7 is able to reduce by 50-90% the numbers of pulmonary metastases in mice bearing murine renal cancer (Renca) or MCA-38 colon adenocarcinoma. Other studies have shown that the antitumor effects of the investigational drug flavone acetic acid (FAA) are also T cell- dependent. However, FAA appears to be inactive for the direct stimulation of human leukocytes in vitro which may at least partially explain its lack of activity in human clinical trials. Similar results have been obtained with a series of xanthanone (XAA) derivatives which are structurally related to the flavonoids. These compounds are also potent cytokine inducers in mice but inactive on human cells. Studies remain in progress to find an FAA or XAA analog that will stimulate human leukocytes. Novel molecular mediators of antitumor activity are also under study. Three unique cytostatic serine proteases have been purified to homogeneity and sequenced from lysates of rat RNK leukemia tumor lines. One enzyme cleaves selectively after aspartic acid (Aspase) another cleaves selectively after methionine (Metase), and the third has trypsin-like activity (trypstase). The biological functions of these enzymes are currently being investigated. As an additional approach to cancer treatment, preliminary studies have shown that several mutated forms of fibroblast growth factor-1 (FGF-1) have direct antitumor activity against mouse and human renal cancer lines in vitro, and against murine renal cancer in vivo.
