News about ProBoost Thymic Protein A: Now Licensed As an Injectable Immune Modulator by the USDA

The active protein in the oral product ProBoost was discovered by Dr. Terry Beardsley, PhD, an immunologist engaged in research on the human thymus gland. Prior to 1983, when Beardsley published his ground-breaking discovery of the maturation of T-cells by the thymus, little was known about this butterfly-shaped gland, located in front of the heart and behind the sternum. “Induction of T-Cell Maturation by a Cloned Line of Thymic Epithelium” was considered important enough to be published in the leading scientific journal the Proceedings of the National Academy of Sciences (Oct. 1983;80:6005–6009).

It was the first time that an actual function of the thymus was proved, that being the maturation of certain immune T-cells (CD4 cells) by a particular protein which Beardsley named thymic protein A (TPA). This protein, a large molecule of 50,000 dalton weight, is so potent that its useful dose is measured in micrograms (millionths of a gram).

Further characterization of the immune regulatory potential of TPA, its mode of action, and its distinction from other known cytokines was published by Pfeifer et al. (J Immunol. 1986;136:55), Ogata et al. (J Immunol. 1987;139:2675), and Pfiefer et al. (Fed Proc. 1987;46:763). Thus, this important protein plays an essential role in the proper intrathymic development of a progenitor (CD-4 CD45+ naïve cells (Fareed et al., ARA, Los Angeles, unpublished observation)) of regulatory T-cells (Hoffmann et al. Blood. 2006;108:4260), capable of modulating immune responses to foreign proteins, and immune reactivity to self antigens.

Based upon research conducted by Beardsley demonstrating TPA’s remarkable immune-modulating activity when administered orally to rodents and dogs, as well as preliminary studies in humans, Beardsley obtained a US patent on this new molecule. In 1996, with assistance from George Klabin of Longevity Science, he developed an oral stabilized form of this single protein, currently marketed as a nutritional supplement, ProBoost Thymic Protein A.

Since the initial introduction of the product, additional human studies (Riordan et al. Townsend Lett. 1998;Feb/Mar:78; Rosenbaum et al. J Nutrit Environ Med. 2001;11:241) have further proved its tremendous immune-regulatory effect. Recently, based on studies in several viral diseases, TPA has been approved by the USDA in injectable form as an aid in the treatment of feline leukemia and feline immunodeficiency virus induced diseases in cats, and associated symptoms including opportunistic infection, anemia, granulocytopenia, and thrombocytopenia. It is the first and only veterinary product approved for those indications. This was only possible because the active substance was proved safe, pure, and efficacious.

The Mysterious Thymus Gland

As late as the middle of the 19th century, the thymus gland remained a mystery to physicians and researchers, who considered that it might be a “vestigial” gland. Some newborns with enlarged thymus glands had them surgically removed, resulting in rapid death from lack of proper immunity. Babies born with an absent or hypoplastic thymus gland (DiGeorge syndrome) quickly died from lack of immune function. Interestingly, this author knows of a case wherein TPA has been used on an infant who was missing her thymus, with excellent results and restoration of proper immune function to literally save her life.

It is now understood that the thymus gland is responsible for the differentiation, specialization, maturation, and activation of T-lymphocytes. The thymus is also the primary site of age-related atrophy and decline in immune capability caused by many viruses, including the human immunodeficiency virus (HIV; Hayes SM. Dev Immunol. 1992;2:191; Bonyhadi ML et al. Nature. 1993;363:728.), measles virus (Auwaerter PG et al. J Virol. 1996;70:3734), and many others; for example cytomegalovirus, a herpes virus (Numazaki K et al. Microbiol Immunol. 1989;33:733). Immune dysfunction may result from the lack of or alteration of specific thymic proteins required for maintaining optimal immune reactivity. This condition occurs as the thymus shrinks, which begins as early as the 20s, and by age 40 the gland is much smaller, eventually often reaching a pealike size by the 60s. As the gland shrinks, it emits less and less thymic protein A, and it is logically theorized that the lack of sufficient TPA is a major contributor to a weakened immune response, since TPA is needed to mature new CD4 (T4) immune cells, as well as to “refresh” the memory of existing ones. Without sufficient TPA, CD4 cell function may be compromised.

How It Works

TPA functions like the operating system software for a computer, and the main CD4 immune cell that it refreshes is known as the “brain” of the white blood cell immune system, as its function is to “regulate” immunity by secreting messenger molecules such as interleukin and interferon, which in turn control other white blood cells such as CD-8 killer cells, NK cells, and macrophages. Because it does not merely stimulate immunity, but rather up- or downregulates as necessary, TPA is valuable in both immune and autoimmune conditions. With the fairly recent understanding that low-level inflammation is connected with most, if not all, degenerative disease, an agent such as TPA that can safely help reduce such inflammation is a very valuable weapon in the arsenal of any practitioner. And for this reason new research is under way with arthritic inflammation in dogs, as is explained later in this article.

How It Is Made

Subsequently, Beardsley formed a company, T-Cyte Therapeutics, which derived the analogous cells and protein from bovine thymus for use in enhancing immune responses to viruses in humans. In his successful patent, Beardsley was able to produce ProBoost TPA in the laboratory by growth and filtration from the epithelial portion of a single bovine thymus, to yield only the active molecule, which is then freeze-dried and mixed, at a dose of only 4 micrograms per packet, with 500 milligrams of maltodextrin.

Studies and Results

Several preclinical studies were performed and the results were recently published (Gingerich D. Intern J Appl Res Vet Med. 2008; 6:61). Initially, it was demonstrated that the protein could boost the neutralizing antibody response 5-fold to rabies virus in dogs, thus increasing protection. A follow-up challenge study was performed which indicated that the protein could double the potency of a standard rabies vaccine and increased survival. In another study with juvenile dogs whose immune systems are not fully developed, an immunization and challenge study was performed with standard distemper vaccine alone versus vaccine plus the protein. The protein doubled the protection from 43% to 86%. No adverse effects of the protein were observed in the young dogs.

The studies suggested that TPA could be used as an immunotherapeutic for treatment of immunocompromised hosts. Therefore, FIV and/or FeLV-infected cats were chosen as preclinical models of human immunodeficiency virus (HIV) disease. After an initial mild, transient leukopenia, fever, and lymphadenopathy, remission occurred for 4 to 5 years. The viruses infect CD-4 positive helper cells, which causes a drop in white blood cell (WBC) count and an increased susceptibility to opportunistic infection. A field study of natural infection was performed. Data were collected initially from 23 infected cats, which met the criteria of the protocol of this study. Enrollment requirements were single infection and at least 2 of the common symptoms of FIV/FeLV infection. A pretreatment blood sample was obtained. An initial inoculation (1cc, (1µg)) was given subcutaneously on day 0. Two subsequent injections were given two weeks apart, day 14 and day 28. A blood sample was taken before the last injection, and lymphocyte levels were compared with pretreatment levels. Cats were chronically and seriously ill when presented to the clinic by the owners. Some were brought in to be euthanized. FIV/FeLV diagnosis was confirmed by laboratory antibody test (IDDEX). Most of the cats were lymphopenic either by differential or by absolute lymphocyte determination. Many were also anemic, some severely (hematocrits 8%–12%). Two were also granulocytopenic. As observed in a preliminary study, cats improved significantly within 72 hours, as reported by the owners, and confirmed by the practitioners upon the second visit two weeks later. At 4 weeks, a second blood sample was taken before the third injection of the initial three-dose regimen. Data from 23 animals were accumulated, and the efficacy of LTCI therapy was based upon absolute lymphocyte counts and improvement in clinical symptoms. Lymphocyte counts increased an average of 38% post treatment. Lymphocyte data were determined to be significant by a paired two-sample student’s t-test.

USDA License Issued

Based upon the forgoing studies, T-Cyte Therapeutics was awarded a license for the protein and assigned the true name Lymphocyte T-Cell Immunomodulator (LTCI) to reflect its mode of action as “an aid in the treatment of FeLV and/or FIV disease and associated symptoms …” It enhances the immune status of FIV/FeLV-infected cats, resulting in a corresponding, significant improvement in the clinical symptoms. The therapeutic effect after 5 years of in-field use appears to be long lasting, and no significant adverse effects have been observed.

In 2006, worldwide concern about a pandemic arose after several deaths in Southeast Asia from an H5N1 strain of influenza in birds were reported. Because of LTCI’s profound immune-modulating properties, T-Cyte’s parent company, S-Cell Biosciences Inc., contracted with a laboratory expert in influenza, Retroscreen Virology in England, to conduct a study of LTCI in ferrets experimentally infected with a laboratory strain of H5N1 influenza virus. Ferrets are the preferred animal model for influenza studies because the pathology of the infection and the immune response to it are similar to that of humans. One concern of the investigators was that a vigorous enhancement of the immune response, especially the cell-mediated immune component, may exacerbate the immunopathology of the infection, since an influx of lymphocytes into the respiratory tract in response to virus is the cause of lung congestion and possible death. In fact, it is believed that in the 1918 worldwide pandemic, more young people died from that strain of influenza because of a more robust immune response and sudden influx of lymphocytes into the lungs caused by the “cytokine storm,” the release of myriad chemoattractants and lymphokines.

To the contrary, LTCI treatment resulted in a significant (p-value = 0.029) reduction in upper respiratory cell counts, as determined in nasal wash fluid (Figure 1). The results were both statistically and clinically significant, since as noted, the immunopathology of influenza is a result of an influx of lymphocytes into the respiratory tract. In addition, viral titers were negative, weight loss was less, and symptom scores were lower in the treatment group compared with the placebo group. Thus, the study further demonstrated that LTCI modulates an effective immune response, while limiting tissue damage caused by an uncontrolled release of cytokines.

Figure 1

This striking result encouraged T-Cyte to test LTCI in another disease wherein the immunopathology is caused by the influx of lymphocytes. The initial thought was osteoarthritis (OA), an affliction affecting 20% of the adult canine population (Morris Animal Foundation) and for which current best practices include the use of nonsteroidal anti-inflammatory drugs (NSAIDS), which are often problematic, especially in older animals; surgery; or even euthanasia when mobility and quality of life are severely compromised. A double-blind study in dogs was conducted by a veterinary orthopedic expert in Kansas City, Missouri. The clinical results were highly significant and correlated with normalization of immune parameters. Data have been submitted for approval of this new indication for LTCI in dogs. In addition a new patent was issued in August 2012 for use of the protein as a method to treat inflammation.

For more information on Thymic Protein A, please contact Longevity Science at

800-933-9440 (in New York), or e-mail George Klabin at GKlabin@mindspring.com