What are the uses of Thymosin alpha 1 (immunomodulator)?

Thymosin Alpha 1: Clinical Uses and Applications

Primary Approved Indications

Thymosin alpha 1 (Tα1) is a synthetic 28-amino acid immunomodulatory peptide approved for treating chronic hepatitis B and C viral infections, and as a vaccine response enhancer in immunocompromised populations. 1, 2

• Chronic Hepatitis B and C: Tα1 has regulatory approval in multiple countries for treating viral hepatitis by enhancing T-cell mediated immune responses 2, 3
• Vaccine Enhancement: Approved to augment vaccine responses in patients with compromised immune function 1, 2

Emerging Oncology Applications

In cancer treatment, Tα1 demonstrates significant survival benefits in specific malignancies, particularly as adjuvant therapy in surgically resectable tumors. 1

• Non-Small Cell Lung Cancer (NSCLC): Significantly improves overall survival in surgically resectable NSCLC when used in the adjuvant setting 1
• Hepatocellular Carcinoma: Shows survival benefit in surgically resectable liver cancers as adjuvant therapy 1
• Locally Advanced NSCLC: In unresectable disease, Tα1 reduces chemoradiation-induced lymphopenia and pneumonia with trending OS improvement 1
• Immune Checkpoint Inhibitor Combinations: Preclinical evidence suggests Tα1 may enhance ICI efficacy by converting "cold tumors" to "hot tumors" and reducing ICI-induced colitis 1

Severe Infections and Sepsis

Tα1 restores immune function and reduces mortality in severe sepsis by reversing sepsis-induced immunosuppression. 4, 1, 2

• Severe Sepsis: A prospective randomized controlled pilot study demonstrated efficacy when combined with ulinastatin in patients with severe sepsis 4
• Mechanism in Sepsis: Addresses the immunosuppression phase that occurs after initial inflammatory response, helping fight primary infections and prevent secondary nosocomial infections 1
• COVID-19: Received emergency use authorization during SARS and COVID-19 pandemics in China as an immune regulator 1, 2

HIV-1 Infection

In HIV-1 infected patients, Tα1 addresses persistent immune dysfunction despite antiretroviral therapy by restoring immune homeostasis and enhancing cytotoxic T-cell responses. 5

• Immune Reconstitution: Helps overcome immunological unresponsiveness and persistent inflammatory conditions that persist despite effective antiretroviral therapy 5
• T-Cell Function: Enhances inefficient cytotoxic T-cell responses commonly seen in HIV patients on long-term therapy 5

Mechanism of Action

Tα1 functions as a biological response modifier that activates multiple immune cell types through Toll-like receptor (TLR) signaling pathways. 1, 2, 3

• TLR Interactions: Binds to TLR2, TLR3, TLR4, TLR7, and TLR9, activating downstream IRF3 and NF-κB signaling pathways 3
• Immune Cell Effects: Influences T cells, B cells, macrophages, and natural killer cells to enhance both innate and adaptive immunity 1, 3
• Macrophage Polarization: Reverses efferocytosis-induced M2 macrophage polarization via TLR7/SHIP1 axis activation, enhancing anti-tumor immunity 1

Clinical Considerations and Safety

Tα1 demonstrates exceptional safety with decades of clinical use, making it suitable for combination with other immunotherapies. 1, 2

• Safety Profile: Long-standing clinical use shows minimal adverse effects across multiple indications 1, 5
• Dosing Limitation: The original peptide has a short plasma half-life requiring frequent dosing, though PASylated formulations extend half-life by 8-fold 6
• Combination Therapy: The favorable safety profile supports exploration in combination with immune checkpoint inhibitors and other cancer immunotherapies 1

Geographic Availability

Regulatory approval and clinical use patterns vary significantly by region. 1, 2

• China: Widely utilized for cancer, severe infections, and as emergency treatment during viral pandemics 1
• International: Approved in various countries for hepatitis B/C and vaccine enhancement, with more limited oncology applications outside China 1, 2