Description of the potential effects of Thymosin-α1 based on the literature. (This is not a product description, disclaimer at the bottom of the page)
Cancer often disrupts the immune system and helps tumors avoid attack, limiting the effectiveness of many treatments. Importantly, many solid tumors, including hepatocellular carcinoma (HCC), melanoma and advanced gastrointestinal or thoracic cancers, create a highly immunosuppressive environment that undermines the effects of targeted drugs, checkpoint inhibitors and standard chemotherapy. Thymosin-α1 (Tα1), a peptide consisting of 28 amino acids and naturally produced by the thymus gland, has long been known for its ability to restore and balance the immune response. Notably, it promotes the maturation of dendritic cells, enhances T-cell activation, boosts natural killer (NK) cell function, and alters cytokine signaling for a more effective anti-tumor response. These activities have made Tα1 an attractive addition to both traditional and modern anticancer therapies.
Research on thymosin-α1 for human cancer treatment
Clinical evidence now suggests that Tα1 can significantly improve treatment outcomes when combined with targeted therapies and immune checkpoint-based therapies. For example, in clinical trials, the addition of Tα1 to lenvatinib and the PD-1 inhibitor sintilimab in patients with advanced HCC extended overall survival from 11 to 16 months and progression-free survival from 4 to 7 months, without increasing treatment-related side effects. Similarly, the use of Tα1 after curative surgery for hepatitis B-related HCC reduced recurrence rates and prolonged survival. In addition to liver cancer, Tα1 enhanced tumor response in combination with dacarbazine and interferon-α in melanoma .
Improves survival rate in advanced liver cancer
Thymosin-α1 (Tα1) can prolong both overall survival and disease progression-free survival when added to standard targeted therapy and immunotherapy for liver cancer. Yao et al (2025) conducted a real-world study in patients with inoperable hepatocellular carcinoma (HCC), comparing lenvatinib in combination with sintilimab, used alone or in combination with Tα1. Importantly, the addition of Tα1 increased overall survival from 11 to 16 months (p = 0.018) and prolonged disease progression-free survival from 4 to 7 months (p = 0.006). In addition, the percentage of objective responses increased from 34.7% to 55.8% (p = 0.042), and the percentage of disease control showed an increasing trend (76.7% vs. 59.2%, p = 0.073). Importantly, the incidence of adverse effects, both mild and severe, was similar in both groups (p > 0.05), indicating the absence of additional Tα1 toxicity [1].
Reduces the risk of recurrence and prolongs life
The use of thymosin-α1 (Tα1) after liver cancer resection can reduce the risk of recurrence and improve long-term survival. He et al (2021) conducted a retrospective analysis of 468 patients with hepatitis B-related HCC who underwent surgical resection. Importantly, Tα1 was associated with better recurrence-free survival (RFS) and overall survival (OS) both before and after statistical adjustment for baseline differences (before adjustment: RFS p = 0.018, OS p < 0.001; after matching: RFS p = 0.006, OS p < 0.001). In addition, multivariate analysis confirmed that Tα1 was an independent predictor of improved outcomes (OS risk ratio [HR] = 0.308, 95% CI 0.175-0.541, p < 0.001; RFS HR = 0.381, 95% CI 0.229-0.633, p < 0.001). Importantly, Tα1 improved immune function, while control of hepatitis B after 24 months remained similar in both groups, suggesting that the survival benefit was mainly due to stronger immune regeneration [2].
Enhances tumor response
Adding thymosin-α1 (Tα1) to dacarbazine-based treatment regimens can improve tumor shrinkage and prolong the duration of response in advanced melanoma. Maio et al (2010) conducted a randomized trial involving 488 patients, testing dacarbazine (DTIC) with or without interferon-α and Tα1 (3.2 mg). Importantly, the two Tα1-containing regimens, DTIC + IFN-α + Tα1 and DTIC + Tα1, induced a greater tumor response (10 and 12) compared to the DTIC + IFN-α control group (4). Moreover, the response lasted longer with Tα1 (up to 23.2 months) than with the control treatment (up to 8.4 months). Although the improvement in overall survival time (9.4 vs. 6.6 months; HR = 0.80, p = 0.08) and disease progression-free survival time (HR = 0.80, p = 0.06) did not reach statistical significance, it should be noted that safety was comparable in all groups and no additional toxicity was observed [3].
Shows activity in difficult-to-treat cancers
Combining thymosin-α1 (Tα1) with focused radiation and immune stimulators can help control advanced cancers that have been resistant to previous therapies. Yu et al (2025) treated 37 patients who underwent intensive therapy with hypofractionated radiation therapy (HFRT) in combination with Tα1 (twice weekly), granulocyte-macrophage colony-stimulating factor (GM-CSF) and the PD-1 inhibitor camrelizumab. Importantly, the objective response rate was 23.1%, and the disease control rate was 65.4%. The median disease progression-free survival time was 3.5 months (95% CI 2.73-4.23). Interestingly, 6 patients (23.1%), including 4 with partial response, had an abscopal effect, i.e. tumor shrinkage outside the radiation field. In addition, patients with a lower neutrophil-to-lymphocyte ratio had a lower risk of metastasis and death (p = 0.024). Based on these results, the regimen was generally well tolerated, with six grade 3-4 adverse effects and no treatment-related deaths [4].
Increases the effectiveness of chemotherapy and immunotherapy
The addition of thymosin-α1 (Tα1) to combination treatment with chemotherapy and immunotherapy improved tumor response in advanced melanoma. Lopez et al (1994) treated 46 patients with a three-drug "biochemotherapy" regimen. Each cycle included dacarbazine (DTIC 850 mg intravenously on day 1), Tα1 (2 mg subcutaneously on days 4-7) and a high dose of interleukin-2 (IL-2, 18 million units/m² per day intravenously on days 8-12), repeated every three weeks. Importantly, of the 42 patients who could be evaluated, 36% responded to treatment: two had complete disappearance of the tumor, and several others had partial tumor reduction. In addition, disease stabilization was maintained in five patients. The median time to tumor progression (progression-free survival time, PFS) was 5.5 months, and the median overall survival time was 11 months. It is worth noting that most of the side effects were due to IL-2 administration, including fever, fatigue and low blood pressure, but Tα1 did not cause additional toxicity. Immunological studies suggested that patients who responded to treatment had lower levels of soluble CD4 (sCD4) and higher levels of soluble CD8 (sCD8) before treatment, indicating that immune balance before treatment may predict benefit [5].
Improves immunity and reduces complications
The use of thymosin-α1 (Tα1) in the perioperative period for colorectal cancer improved immune system recovery, reduced infections and lowered the risk of tumor recurrence. Niu et al (2024) studied 400 patients with colon or rectal cancer scheduled for surgery followed by XELOX (capecitabine plus oxaliplatin) chemotherapy. Patients were randomly assigned to receive XELOX chemotherapy alone or XELOX chemotherapy in combination with thymalfascin (Tα1) at a dose of 1.6 mg administered subcutaneously two or three times a week. Importantly, both groups receiving Tα1 had fewer postoperative infections, better T-cell recovery after surgery, and lower rates of early and late complications compared to the group receiving chemotherapy alone (all p < 0.05). In addition, the rate of tumor recurrence and spread was reduced, and relapse-free survival improved. Interestingly, the twice-weekly regimen was as effective as the thrice-weekly regimen, offering a simpler dosing option. Side effects remained mild and were similar in all groups [6].
Rebuilds immunity and improves survival rate
Thymosin-α1 (Tα1) helped restore immune function and improved outcomes in patients with non-small cell lung cancer (NSCLC) after radiation therapy. Schulof et al (1985) randomly assigned 42 patients with radiation-induced immunosuppression to a group receiving either placebo or synthetic Tα1. Two dosing regimens were tested: a saturating dose regimen and a fixed twice-weekly regimen. Importantly, no restoration of immunity was observed in the placebo-treated patients at 15 weeks. In contrast, Tα1 restored T-cell function with the saturating dosing regimen (p = 0.04) and maintained a normal percentage of T helper cells with the twice-weekly dosing regimen (p = 0.04). In addition, patients who received Tα1 reported better relapse-free survival and overall survival , especially those with smaller, less extensive tumors. The treatment was well tolerated, with only mild local reactions reported [7].
Animal studies of thymosin-α1 in cancer treatment
Prevents the spread of cancer and improves survival rates
Thymosin-α1 (Tα1) protected the weakened immune system from tumor spread and shortened survival in preclinical cancer models. Ishitsuka et al (1983) studied mice whose immunity had been weakened by chemotherapy or x-ray exposure, and then exposed them to B16 melanoma or L1210 leukemia cells. Importantly, untreated mice developed a rapid increase in lung metastasis and died more quickly, but Tα1 treatment prevented this increase and prolonged survival. Mechanistic experiments showed that natural killer (NK) cells played a key role in this protection. Tα1 preserved NK cell activity, and adoptive transfer studies confirmed that the protective effect was due to spleen cells containing NK cells, not T cells. In addition, Tα1 corrected abnormal tumor cell movement caused by the chemotherapeutic drug 5-fluorouracil (5-FU). In untreated animals, 5-FU caused tumor cells to accumulate in the blood and lungs, while decreasing their numbers in the liver and spleen. With Tα1, this pattern of cell movement returned to normal, helping to maintain natural immune barriers and reduce metastasis [8].
Strengthen immunity and inhibit cancer growth
Brief therapy with thymosin-α1 (Tα1) activated the immune system, slowed tumor growth and reduced metastasis in a mouse model of cancer. Beuth et al (2000) implanted tumors into BALB/c mice and administered Tα1 once a day for seven days at doses ranging from 0.01 to 10 μg per mouse subcutaneously, starting 24 hours after tumor implantation. Importantly, on day 14, Tα1-treated mice had higher thymocyte counts and more circulating immune cells, indicating a clear activation of the immune system. In addition, tumor outcomes improved: treated mice had fewer liver and lung metastases, and primary tumors were smaller compared to untreated control mice (p < 0.05). Importantly, no safety concerns were reported, even at higher doses. Taken together, these results demonstrate that a brief pulse of Tα1 can mobilize host defense mechanisms, shrink tumors and limit tumor spread [9].
Strengthens immune attack and prolongs survival rate
Adding thymosin-α1 (Tα1) to hyperthermic intraperitoneal chemotherapy (HIPEC) slightly improved survival and enhanced anti-tumor immunity in a colon cancer model. Nevo et al (2022) used mice with peritoneal metastases from colorectal cancer. After HIPEC treatment with mitomycin C ( ), the animals received Tα1 at a dose of 0.6 mg/kg subcutaneously for five consecutive days. Importantly, survival improved compared to HIPEC alone (16.1 ± 0.8 days vs. 14.1 ± 0.6 days; p = 0.02). Mechanistic tests showed that Tα1 did not directly kill tumor cells, but altered the immune response toward Th1 activity. Levels of interferon-γ (IFN-γ) and the transcription factor T-bet increased, and CD8⁺ T-cell infiltration increased in both network and visceral metastases - both changes were highly significant. These findings indicate that Tα1 promotes tumor control after surgical therapy by enhancing the immune response, rather than acting as a chemotherapeutic drug [10].
Reverses immune suppression to improve cancer therapy
Thymosin-α1 (Tα1) helped restore anti-tumor immunity and increased the efficacy of oncolytic virus treatment. Liu et al (2024) investigated how oncolytic adenovirus (ADV), although capable of killing tumor cells, can sometimes induce immune suppression inside the tumor. Importantly, ADV therapy pushed tumor-associated macrophages toward a tumor-promoting M2 state and attracted more regulatory T (Treg) cells, which dampen tumor-fighting immune activity. To counteract this, the researchers administered Tα1 in two ways: by direct injection or by modifying the virus itself to secrete Tα1 (ADV^Tα1). Interestingly, both strategies reprogrammed macrophages away from the M2 state, promoted a Th1-oriented immune response, and increased infiltration and activation of CD8⁺ killer T cells inside tumors. As a result, these immune changes restored potent anti-tumor activity and significantly increased the efficacy of oncolytic virus therapy. Importantly, the addition of Tα1 did not raise any new safety concerns. The results show that Tα1 can lift the immune "brakes" induced by viral therapy, turning oncolytic viruses into more potent and precise cancer-fighting agents [11].
Enhances combinations of multiple liver cancer drugs
Thymosin-α1 (Tα1) has enhanced a complex treatment strategy to improve survival and reduce tumor growth in liver cancer. Fu et al (2015) used a rat model of diethylenitrosamine (DEN)-induced hepatocellular carcinoma (HCC) to test a triple therapy. The treatment regimen included: Tα1 at a dose of 0.8 mg/kg administered subcutaneously daily for two weeks and then twice weekly thereafter, Huaier granules (a traditional herbal medicine with anti-tumor effects) and sirolimus (an mTOR inhibitor that blocks the growth and survival of cancer cells). The treatment lasted 20 weeks. Importantly, the triple combination provided better survival, reduced the incidence of cancer, and significantly reduced serum alpha-fetoprotein (AFP) levels, a marker of liver cancer, compared to any single drug or double combination. Immunological tests showed that Tα1 broadly enhanced the immune response, Huaier showed direct anti-tumor effects, and sirolimus blocked metabolic pathways that promote tumor growth. Combining these three drugs in a " " approach allowed attacking both cancer cells and the tumor-promoting microenvironment, demonstrating how Tα1 can enhance the effects of targeted and metabolic therapies when used as part of a combination strategy [12].
Dosage of thymosin α1 in cancer treatment
Thymosin-α1 (Tα1) is usually administered subcutaneously, with most cancer studies using a dose of 1.6 mg twice a week for several months, although some studies have tested higher or more intensive dosing regimens. Importantly, the most common dosing regimen in clinical trials has been 1.6 mg twice a week, but doses of 3.2 mg and sometimes even 6.4 mg have also been studied. Lopez et al (1994) treated metastatic melanoma with 2 mg of Tα1 injected on days 4-7 of each 21-day cycle, in combination with dacarbazine (DTIC 850 mg intravenously on day 1) and high-dose interleukin-2 (IL-2, 18 million units/m² per day intravenously on days 8-12). In addition, Maio et al (2010) studied Tα1 at doses of 1.6-6.4 mg in combination with dacarbazine, with or without interferon-α, for up to 12 months. In colorectal cancer surgery, Niu et al (2024) compared a dose of 1.6 mg twice a week with a more frequent regimen of three times a week administered perioperatively and XELOX chemotherapy (capecitabine plus oxaliplatin). Interestingly, the increased dosing frequency did not result in additional benefit, suggesting that twice a week may be sufficient. In restoring immunity after radiotherapy, Schulof et al (1985) tested both a saturating dose and a fixed twice-weekly regimen for about 15 weeks in non-small cell lung cancer. Tα1 restored T-cell function compared to placebo. Based on clinical trials, although the 1.6-mg twice-weekly dose remains the most common and practical regimen, higher doses or alternative treatment regimens have been tested in some cancers, but without consistent evidence that they are superior to the standard approach.
Disclaimer
This article was written for educational purposes and is intended to raise awareness of the substance under discussion. It is important to note that the article is about the substance in general - it is not a description of a specific product (chemical reagent). We do not suggest the use of chemical reagents on humans - this is prohibited by law, for a product to be used for treatment it must be registered as a drug. The information contained in the text is based on available scientific research and is not intended to serve as medical advice or promote self-medication. The reader should consult any health and treatment decisions with a qualified health professional.
References
- Yao, S., Huang, Q., Zou, Y., Liu, T., Yang, Y., Huang, T., Zhao, Y. and Dong, X. (2025). Efficacy and safety of thymosin alfa-1 in combination with lenvatinib and sintilimab in inoperable hepatocellular carcinoma: a retrospective study. Scientific Reports, 15(1), 13960. https://doi.org/10.1038/s41598-025-97160-7 https://pubmed.ncbi.nlm.nih.gov/40263352/
- He, L., Xia, Z., Peng, W., He, C., Li, C. and Wen, T. (2021). Thymosin alpha-1 therapy improves postoperative survival after curative resection of single hepatitis B virus-associated hepatocellular carcinoma: a propensity matching analysis. Medicine (Baltimore), 100(20), e25749. https://doi.org/10.1097/MD.0000000000025749 https://pubmed.ncbi.nlm.nih.gov/34011034/
- Maio, M., Mackiewicz, A., Testori, A., Trefzer, U., Ferraresi, V., Jassem, J., Garbe, C., Lesimple, T., Guillot, B., Gascon, P., Gilde, K., Camerini, R., Cognetti, F. and Thymosin Melanoma Investigation Group. (2010). Large randomized trial on the use of thymosin alfa 1, interferon alfa or both in combination with dacarbazine in patients with metastatic melanoma. Journal of Clinical Oncology, 28(10), 1780–1787. https://doi.org/10.1200/JCO.2009.25.5208 https://pubmed.ncbi.nlm.nih.gov/20194853/
- Yu, J., Yin, L., Guo, W., Wang, Q., Liu, J., Zhang, L., Ye, H., Xia, J., Xia, Y., Wu, J., Wang, W., Yang, Y., Zong, D., He, X., Wang, L., Jiang, H. (2025). Hypofractionated radiotherapy in combination with PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor, and thymosin-α1 in advanced metastatic solid tumors: a multicenter phase II clinical trial. Cancer Immunology, Immunotherapy, 74(3), 98. https://doi.org/10.1007/s00262-024-03934-9 https://pubmed.ncbi.nlm.nih.gov/39904914/
- Lopez, M., Carpano, S., Cavaliere, R., Di Lauro, L., Ameglio, F., Vitelli, G., Frasca, A. M., Vici, P., Pignatti, F., Rosselli, M., et al. (1994). Biochemotherapy with thymosin alpha 1, interleukin-2 and dacarbazine in patients with metastatic melanoma: clinical and immunologic effects. Annals of Oncology, 5(8), 741-746. https://doi.org/10.1093/oxfordjournals.annonc.a058979https://pubmed.ncbi.nlm.nih.gov/7826907/
- Niu, W., Li, Z., Li, Z., Hu, X., Wang, X., Ding, Y., Li, C., and Yu, B. (2024). A prospective and randomized controlled trial on the effect of thymalfascin for injection on perioperative immune function and long-term prognosis in patients with colorectal cancer. Biotechnol Genet Eng Rev, 40(4), 4862-4874. https://doi.org/10.1080/02648725.2023.2216972 【PMID: 37248723】 https://pubmed.ncbi.nlm.nih.gov/37248723/
- Schulof, R. S., Lloyd, M. J., Cleary, P. A., Palaszynski, S. R., Mai, D. A., Cox, J. W. Jr., Alabaster, O., and Goldstein, A. L. (1985). Randomized trial evaluating the immunodevelopment properties of synthetic thymosin alpha 1 in patients with lung cancer. Journal of Biological Response Modifiers, 4(2), 147-158. PMID: 3998766 https://pubmed.ncbi.nlm.nih.gov/3998766/
- Ishitsuka, H., Umeda, Y., Sakamoto, A., and Yagi, Y. (1983). Protective effect of thymosin alpha 1 against tumor progression in immunocompromised mice. Advances in Experimental Medicine and Biology, 166, 89-100. https://doi.org/10.1007/978-1-4757-1410-4_9 【PMID: 6650286】 https://pubmed.ncbi.nlm.nih.gov/6650286/
- Beuth, J., Schierholz, J. M., and Mayer, G. (2000). Thymosin alpha(1) application enhances the immune response and reduces tumor weight and organ colonization in BALB/c mice. Cancer Letters, 159(1), 9-13. https://doi.org/10.1016/s0304-3835(00)00510-3 【PMID: 10974400】https://pubmed.ncbi.nlm.nih.gov/10974400/
- Nevo, N., Goldstein, A. L., Bar-David, S., Natanson, M., Alon, G., Lahat, G., and Nizri, E. (2022). Thymosin alpha 1 as an adjuvant to hyperthermic intraperitoneal chemotherapy in an experimental model of peritoneal metastasis from colorectal cancer. International Immunopharmacology, 111, 109166. https://doi.org/10.1016/j.intimp.2022.109166. PMID: 35994852 https://pubmed.ncbi.nlm.nih.gov/35994852/
- Liu, K., Kong, L., Cui, H., Zhang, L., Xin, Q., Zhuang, Y., Guo, C., Yao, Y., Tao, J., Gu, X., Jiang, C. and Wu, J. (2024). Thymosin α1 reverses M2 macrophage polarization induced by oncolytic adenovirus, improving anti-tumor immunity and therapeutic efficacy. Cell Reports Medicine, 5(10), 101751. https://doi.org/10.1016/j.xcrm.2024.101751. PMID: 39357524; PMCID: PMC11513825. https://pubmed.ncbi.nlm.nih.gov/39357524/
- Fu, X., Wei, Y., Zheng, D., Zhou, L., Zhu, Z., Song, J., Feng, L. and Du, G. (2015). [Thymosin α-1-based triple anticancer therapy reduces liver cancer incidence and serum alpha-fetoprotein levels in a rat model of liver cancer]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 31(6), 744-748. PMID: 26062414. https://pubmed.ncbi.nlm.nih.gov/26062414/