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

J. L. Murray, J. M. Reuben, T. L. Smith, E. A. Gehan, S. M. Koretz, Evan M Hersh

Research output: Contribution to journalArticle

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Abstract

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 < 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 < 0.05), OKT8 positive suppressor cells (179 ± 186 to 279 ± 184; p < 0.05), and surface immunoglobulin-bearing B cells (49 ± 47 to 155 ± 268; p < 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 scheduled.

Original languageEnglish (US)
Pages (from-to)56-68
Number of pages13
JournalJournal of Biological Response Modifiers
Volume6
Issue number1
StatePublished - 1987
Externally publishedYes

Fingerprint

TCF Transcription Factors
Clinical Trials
Neoplasms
Lymphocytes
Prealbumin
Lymphocyte Subsets
Skin Tests
B-Lymphocytes
Phytolacca americana
T-Lymphocytes
Lymphocytosis
B-Cell Antigen Receptors
Immunologic Tests
Delayed Hypersensitivity
Phytohemagglutinins
Subcutaneous Injections
Esophageal Neoplasms
Head and Neck Neoplasms
Lymphocyte Activation
Concanavalin A

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

A pilot clinical trial of the toxicity and immunorestorative effects of T cell reconstituting factor (SR 270258) in immunosuppressed cancer patients. / Murray, J. L.; Reuben, J. M.; Smith, T. L.; Gehan, E. A.; Koretz, S. M.; Hersh, Evan M.

In: Journal of Biological Response Modifiers, Vol. 6, No. 1, 1987, p. 56-68.

Research output: Contribution to journalArticle

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abstract = "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 < 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 < 0.05), OKT8 positive suppressor cells (179 ± 186 to 279 ± 184; p < 0.05), and surface immunoglobulin-bearing B cells (49 ± 47 to 155 ± 268; p < 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 scheduled.",
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