A pilot clinical trial of the toxicity and immunorestorative effects of T cell reconstituting factor (SR 270258) in immunosuppressed cancer patients.

The in vivo immunorestorative effects of a highly purified protein fraction from human serum--designated SR 270258, prealbumin, or T cell reconstituting factor--was examined in cancer patients following radiation therapy. Sixteen patients with either Stage III head and neck cancer, nonoat cell lung cancer, or esophageal cancer were randomized to either receive (11 patients) or not receive (five patients) subcutaneous injections or SR 270258 at a dose of 2 mg/m2 three times per week for a total duration of 1 month. Treated patients were observed frequently for signs of toxicity. Blood was drawn initially and at weekly intervals for measurement of immunologic tests, which included percentage and absolute number of T cells, B cells, and other lymphocyte subpopulations; lymphocyte blastogenic responses to the mitogens phytohemagglutinin, concanavalin A, and pokeweed; and one-way mixed lymphocyte responses. Delayed type hypersensitivity responses to seven recall antigens were also tested. Mean lymphocyte blastogenic responses were significantly suppressed in patients relative to normal (p less than 0.05). There were no consistent changes in lymphocyte blastogenic responses, the percentage of lymphocyte subpopulations, or skin test responses in patients receiving SR 270258 versus untreated patients. However, the absolute number of OKT11 positive (E rosette receptor positive) T lymphocytes increased a mean of 52% (406 +/- 356 to 617 +/- 344/mm3; p = 0.03) in treated patients whereas no change was observed in untreated patients (366 +/- 226 to 446 +/- 327). Significant increases in the absolute number of OKT4 positive helper cells (158 +/- 109 to 221 +/- 112; p less than 0.05), OKT8 positive suppressor cells (179 +/- 186 to 279 +/- 184; p less than 0.05), and surface immunoglobulin-bearing B cells (49 +/- 47 to 155 +/- 268; p less than 0.05) also occurred. Prealbumin can induce a significant lymphocytosis in heavily irradiated, lymphopenic cancer patients. Lymphocyte blastogenesis and skin tests, however, were not improved at this dose and schedule.