Review
10.1517/14712590902911412©2009InformaUKLtdISSN1471-2598 593
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Fromlabtobedside:emerging
clinicalapplicationsofthymosinα
1
Allan L Goldstein
†
& Adam L Goldstein
*
†
The George Washington University School of Medicine and Health Sciences, Washington DC, USA
*Medical School for International Health at Ben-Gurion University of the Negev, Be’er Sheva, Israel
Background: Thymosin α
1
(Tα
1
), a synthetic version of a thymic-derived
biological response modifier was the first of the thymosins in clinical use.
Tα
1
is approved in over 35 countries for the treatment of hepatitis B and C,
and as an immune stimulant and adjuvant. Tα
1
is also in late-stage clinical
testing in the United States and Europe for hepatitis C and stage IV mela-
noma. Objective/methods: Novel applications and other recently completed
trials point to much broader clinical applications of Tα
1
in the treatment of
life-threatening and chronic diseases, and are the subject of this review.
Result/conclusions: The most recent reports of clinical trials with Tα
1
are
pointing to important, hitherto unrecognized, applications in a number of
diseases and disorders, including septic shock, acute respiratory distress syn-
drome, peritonitis, acute cytomegalovirus infection, TB, severe acute respiratory
syndrome, and lung infections in critically ill patients. It is also emerging as
a promising chemoprotection agent in patients undergoing chemotherapy.
Keywords: biological response modifiers, cancer, immune modulation, infectious diseases, T-cells,
thymosin α
1
Expert Opin. Biol. Ther. (2009) 9(5):593-608
1. Introduction
The isolation and chemical characterization of many of the key molecules and
receptors that regulate the immune system and host resistance have now been
performed. These molecules, which include cytokines, chemokines, thymosins
and growth factors, are collectively termed biological response modifiers
(BRMs) [1]. Many of these BRMs, first discovered at the end of the twentieth
century, have now made a successful transition from the lab bench to the clinic
resulting in the creation of a new and rapidly expanding family of immune-based
or adjuvant therapeutics. These synthetic or recombinant forms of natural sub-
stances, based on an understanding of the body’s own immune system, have
provided clinicians with a plethora of potent weapons in the fight against many
life-threatening and debilitating diseases from infectious diseases [2] to cancers [3]
and rheumatic diseases [4]. What has emerged from an analysis of clinical trials
conducted with BRMs over the past decade has been their emergence and recom-
mended use either as first line mono or adjuvant therapies [5-7]. The use of Tα
1
and other BRMs in combination with conventional therapies and/or other BRMs
in order to increase the efficacy of treatment, decrease mortality and lower mor-
bidity currently appears to be more clinically applicable and useful compared with
their use as monotherapies [6,7]. A large number of new applications for BRMs
are being studied, and their full potential in decreasing the length, toxicities and
dosing of current conventional treatments and/or to strengthen the efficacy of
current treatments for a variety of diseases remains to be fully established.
1. Introduction
2. Discovery of the thymosins
3. Pleiotropic properties of
thymosin α
1
4. Mechanism of action
5. Anti-tumor and anti-fungal
properties of tα
1
at the cellular
and molecular level
6. Clinical applications
7. Infectious diseases
8. Cancer
9. Immune deficiencies
10. Boosting vaccine efficacy
11. Conclusions and expert opinion