In vivo immune restoration in advanced cancer patients after administration of thymosin fraction 5 or thymosin alpha 1.

Since patients with advanced cancer are usually immunodeficient, they might benefit from therapy with thymic hormones, which have an immunorestorative effect in immunosuppressed laboratory animals. We treated 14 patients with thymosin fraction 5 (TF5), and 14 patients with thymosin alpha 1 (TA1) over the dose ranges of 60-960 mg/m2 and 0.6-9.6 mg/m2, respectively. In addition to monitoring toxicity, we studied patients extensively using a variety of lymphocyte cell surface markers and in vitro functional assays, both before and following treatment. Approximately one-half of the in vitro tests were abnormal in the cancer patients prior to treatment. Overall, 28.4 and 18.3% of abnormal tests were improved following TA1 and TF5, respectively. On the other hand, 16% of normal tests became abnormal after therapy. Most of these responses occurred within 24-48 h and seldom persisted beyond 72 h. An optimum dose of TF5 was not readily identified, but 1.2 mg/m2 of TA1 was associated with substantial improvement in 46% of abnormal tests. Twelve of 14 cancer patients who received TF5 and 13 of 14 who received TA1 showed significant improvement in at least one in vitro test. Tumor responses were not seen, but the study suggested thymosin treatments would need to be repeated every 2-3 days to sustain an immune response. TF5 and TA1 are well tolerated as single i.m. injections, and have immunorestorative potential in cancer patients. Additional studies with repeated thymosin doses in more homogeneous cancer populations appear to be justified.