TY - GEN
T1 - Thymosin alpha 1
T2 - From bench to bedside
AU - Garaci, Enrico
AU - Favalli, Cartesio
AU - Pica, Francesca
AU - Vallebona, Paola Sinibaldi
AU - Palamara, Anna Teresa
AU - Matteucci, Claudia
AU - Pierimarchi, Pasquale
AU - Serafino, Annalucia
AU - Mastino, Antonio
AU - Bistoni, Francesco
AU - Romani, Luigina
AU - Rasi, Guido
PY - 2007/9
Y1 - 2007/9
N2 - After the initial dramatic effects, observed in a Lewis lung carcinoma animal model, using a combination of thymosin alpha 1 (Tα1) and interferon (IFN) after cyclophosphamide, a number of other preclinical models in mice (Friend erythroleukemia and B16 melanoma) and in rats (DHD/K12 colorectal cancer liver metastasis) have confirmed the efficacy of the combination therapy with Tα1 and either IFN or IL-2 plus chemotherapy. These results provided the scientific foundation for the first clinical trials using Tα1 in combination with BRMs and/or chemotherapy. Pivotal trials in advanced non-small cell lung cancer (NSCLC) and melanoma with Tα1 and IFN-α low doses after cis-platinum or dacarbazine produced the first evidence of the high potentiality of this approach in the treatment of human cancer. The combination of Tα1 and IFN-α was also used in patients affected by chronic B and C hepatitis including IFN-nonresponders and infected by precore mutants or genotype 1b. Further studies demonstrated additional biological activities clarifying the mechanism of action of Tα1, partially explaining the synergism with IFN. It has been shown the capacity of activating infected dendritic cells through Toll-like receptor signaling, thus influencing the inflammation balance, and of increasing the expression of tumor, viral, and major histocompatibility complex (MHC) I antigens. Dose-response studies suggested the possibility of improving the efficacy of this molecule reducing the overall toxic. Based on these information two clinical trials are ongoing: a large phase II on advanced melanoma patients treated with Tα1 at different doses after dacarbazine and a phase III one, on IFN-resistant hepatitis C virus (HCV) patients treated with a triple combination (IFN, ribavirin, and Tα1).
AB - After the initial dramatic effects, observed in a Lewis lung carcinoma animal model, using a combination of thymosin alpha 1 (Tα1) and interferon (IFN) after cyclophosphamide, a number of other preclinical models in mice (Friend erythroleukemia and B16 melanoma) and in rats (DHD/K12 colorectal cancer liver metastasis) have confirmed the efficacy of the combination therapy with Tα1 and either IFN or IL-2 plus chemotherapy. These results provided the scientific foundation for the first clinical trials using Tα1 in combination with BRMs and/or chemotherapy. Pivotal trials in advanced non-small cell lung cancer (NSCLC) and melanoma with Tα1 and IFN-α low doses after cis-platinum or dacarbazine produced the first evidence of the high potentiality of this approach in the treatment of human cancer. The combination of Tα1 and IFN-α was also used in patients affected by chronic B and C hepatitis including IFN-nonresponders and infected by precore mutants or genotype 1b. Further studies demonstrated additional biological activities clarifying the mechanism of action of Tα1, partially explaining the synergism with IFN. It has been shown the capacity of activating infected dendritic cells through Toll-like receptor signaling, thus influencing the inflammation balance, and of increasing the expression of tumor, viral, and major histocompatibility complex (MHC) I antigens. Dose-response studies suggested the possibility of improving the efficacy of this molecule reducing the overall toxic. Based on these information two clinical trials are ongoing: a large phase II on advanced melanoma patients treated with Tα1 at different doses after dacarbazine and a phase III one, on IFN-resistant hepatitis C virus (HCV) patients treated with a triple combination (IFN, ribavirin, and Tα1).
KW - Clinical trials
KW - Preclinical models
KW - Thymosin alpha 1
UR - http://www.scopus.com/inward/record.url?scp=35349030180&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35349030180&partnerID=8YFLogxK
U2 - 10.1196/annals.1415.044
DO - 10.1196/annals.1415.044
M3 - Conference contribution
C2 - 17600290
AN - SCOPUS:35349030180
SN - 1573317012
SN - 9781573317016
VL - 1112
T3 - Annals of the New York Academy of Sciences
SP - 225
EP - 234
BT - Annals of the New York Academy of Sciences
ER -