Lymphocyte T-Cell Immunomodulator

Lymphocyte T-Cell Immunomodulator (LTCI, Lymphocyte T-Cell Immunomodulator) is an immune regulating polypeptide manufactured and distributed by T-Cyte Therapeutics . Lymphocyte T-Cell Immunomodulator is a potent regulator of CD-4 lymphocyte production and function. It has been shown to increase lymphocyte numbers and Interleukin-2 (IL-2) production in animals.

Discovery and Characterization

Prior to 1960 the thymus gland, which lies in the cervical thoracic area, was thought to be of little importance. In adult animals the thymus is almost non-existent because it atrophies as animals reach adulthood. It was observed, however, that when pre-adolescent animals are thymectomized they experience a variety of maladies including increased incidence of infection, failure to grow, neuromuscular disorders, cancer, etc., collectively known as “wasting disease”. The greater susceptibility to infection was shown to be directly attributable to a dramatic decrease in peripheral blood lymphocytes in thymectomized animals.

By 1964 it had been demonstrated that regulatory factors extracted from the thymus gland could prevent many of the manifestations of wasting disease.[1][2] This suggested that the thymus produces substances important in the development of immunity. It was not until 1971 that it was discovered that thymus-derived lymphocytes (T-cells) were important regulators of bone-marrow-derived antibody-producing lymphocytes (B-cells). After the discovery that the thymus was producing profound regulatory factors, several groups of scientists began trying to extract and purify this factor from thymus glands in much the same manner that insulin was prepared from the pancreas for therapeutic use in diabetes. The difficulty was that the thymus is a very small gland and produces very small quantities of the factor. Thus, purification techniques did not allow appropriate pure fractions to be produced in sufficient quantities.

Thymus is a preferred tissue for viral replication of feline immunodeficiency virus, which results in lesions and dysfunction.[3]

In 1983 scientists succeeded in cloning epithelial cell lines from the thymus of various species and began to biochemically and biologically characterize these thymus derived regulatory factors.[4] A protein with a molecular weight of about 50,000 daltons was subsequently described and shown to augment the immune responses of both immature and mature T-cells.[5] This protein came to be known as Lymphocyte T-Cell Immunomodulator (LTCI).

Biological Properties

Generally, a proportion of immature thymus-derived lymphocytes differentiate into mature CD4+ T-cells which produce a certain amount of cytokines, such as interleukin-2 (IL-2) and gamma interferon. To attack tumor cells and viruses, CD-4 cells coordinate the overall immune response and help activate CD8 T-lymphocytes. Often called “effector” or “cytotoxic” T-cells, CD-8+ T-lymphocytes they respond to intracellular pathogens and cancer cells. Under viral attack CD-4+ T-cells fail to mature, fail to produce IL-2 and gamma interferon, and consequently fail to coordinate CD-8 responses to viruses. LTCI increases the production of CD-4+ T-cells and can subsequently overcome this immunosuppression. [6]

Biochemical Properties

Lymphocyte T-Cell Immunomodulator is a single chain polypeptide that is a strongly cationic glycoprotein and is purified with cation exchange resin. Purification of protein from bovine-derived stromal cell supernatants produces a substantially homogeneous factor, free of extraneous materials. The bovine protein is homologous with other mammalian species and is a homogeneous 50 kDa glycoprotein with an isoelectric point of 6.5. The protein is prepared in a lyophilized 1 microgram dose. Reconstitution in sterile diluent produces a solution for subcutaneous injection.[7]

Uses in Veterinary Medicine

Feline Leukemia Virus and/or Feline Immunodeficiency Virus

LTCI is manufactured and distributed exclusively by T-Cyte Therapeutics, Inc. LTCI has been conditionally approved by the United States Department of Agriculture (USDA) as an aid in the treatment of cats infected with feline leukemia virus (FeLV) and/or feline immunodeficiency virus (FIV), and the associated symptoms of lymphopenia, opportunistic infection, anemia, granulocytopenia, or thrombocytopenia. [8]

Canine Osteoarthritis

LTCI increases the immune response to foreign antigens and dampens the immune-mediated response to self-antigens by increasing the number of precursors of a regulatory T-Cell population. In a double-blind placebo-controlled study, 11 of the 12 LTCI-treated canines had a 40 percent increase in function while the placebo group had a 17 percent decrease in function. [9] Following the study, LTCI was approved by the USDA to treat osteoarthritis in dogs in 2016. [10]

Links

  1. ↑ Asanuma Y, Goldstein AL, White A. Reduction in the incidence of wasting disease in neonatally thymectomized CBA-W mice by the injection of thymosin. Endocrinology. 1970 Mar;86(3):600-10.
  2. ↑ Stutman O, Yunis EJ, Martinez C, Good RA. Reversal of post-thymectomy wasting disease in mice by multiple thymus grafts. J Immunol. 1967 Jan;98(1):79-87.
  3. ↑ Woo JC, Dean GA, Pedersen NC, Moore PF. Immunopathologic changes in the thymus during the acute stage of experimentally induced feline immunodeficiency virus infection in juvenile cats. J Virol. 1997 Nov;71(11):8632-41.
  4. ↑ Beardsley, et al. "Induction of T-Cell Maturation by a Cloned Line of Thymic Epithelium (TEPI) Immunology 80: pp. 6005-6009, (Oct. 1983).
  5. ↑ Beardsley, Terry R. Patent # 7,196,060; Method to enhance hematopoiesis.
  6. ↑ Beardsley, Terry R. Patent # 7,196,060; Method to enhance hematopoiesis.
  7. ↑ Beardsley, Terry R. Patent # 7,196,060; Method to enhance hematopoiesis.
  8. ↑ Vetinfo. "Feline Immunodeficincy Virus Treatment with Lymphocyte T-Cell Immunomodulator." Retrieved 18 November 2016.
  9. ↑ "Lymphocyte T-Cell Immunomodulator (LTCI), a Potent Immune Modulating Biologic, Exhibits Safety and Efficacy in the Pain Management of Dogs with Moderate-Severe Osteoarthritis." Retrieved 18 November 2016].
  10. ↑ Marketwired."T-Cyte Launches First USDA-Approved Treatment Aid for Canine Osteoarthritis." Retrieved 18 November 2016.
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