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 tumours to avoid attack, limiting the effectiveness of many treatments. Importantly, many solid tumours, including hepatocellular carcinoma (HCC), melanoma and advanced gastrointestinal or thoracic cancers, create a highly immunosuppressive environment that undermines the effect of targeted drugs, checkpoint inhibitors and standard chemotherapy. Thymosin-α1 (Tα1), a peptide consisting of 28 amino acids, naturally produced by the thymus gland, has long been known for its ability to restore and balance the immune response. Notably, it promotes dendritic cell maturation, enhances T-cell activation, boosts natural killer (NK) cell function and alters cytokine signalling towards a more effective anti-tumour response. These actions have made Tα1 an attractive addition to both traditional and modern anti-cancer therapies.
Research into thymosin-α1 for the treatment of human cancers
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 increased overall survival from 11 to 16 months and progression-free survival from four to seven months, with no increase in 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 tumour response in combination with dacarbazine and interferon-α in melanoma .
Improves survival 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 no additional Tα1 toxicity [1].
Reduces the risk of recurrence and prolongs life
The use of thymosin-α1 (Tα1) after liver cancer resection may 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). Furthermore, multivariate analysis confirmed that Tα1 was an independent predictor of improved outcome (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 hepatitis B control at 24 months remained similar in both groups, suggesting that the survival benefit was mainly due to stronger immune regeneration [2].
Enhances tumour response
The addition of thymosin-α1 (Tα1) to dacarbazine-based treatment regimens may improve tumour shrinkage and prolong response duration in advanced melanoma. Maio et al (2010) conducted a randomised 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 tumour response (10 and 12) compared to the DTIC + IFN-α control group (4). Furthermore, 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 may help control advanced cancers that have been resistant to previous therapies. Yu et al (2025) treated 37 patients who underwent intensive therapy using hypofractionated radiotherapy (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, six patients (23.1%), including four with a partial response, had an abscopal effect, i.e. tumour shrinkage outside the irradiation 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].
Enhances the effectiveness of chemotherapy and immunotherapy
The addition of thymosin-α1 (Tα1) to combined chemotherapy and immunotherapy treatment improved tumour 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 patients had complete tumour disappearance and several others had partial tumour reduction. In addition, disease stabilisation was maintained in five patients. The median time to tumour progression (progression-free survival time, PFS) was 5.5 months and the median overall survival time was 11 months. It is noteworthy 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 tumour recurrence. Niu et al (2024) studied 400 patients with colorectal or rectal cancer scheduled for surgery followed by XELOX (capecitabine plus oxaliplatin) chemotherapy. Patients were randomly allocated 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 regeneration after surgery and lower rates of early and late complications compared to the group receiving chemotherapy alone (all p < 0.05). In addition, the incidence of tumour 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 rates
Thymosin-α1 (Tα1) helped restore immune function and improved outcomes in patients with non-small cell lung cancer (NSCLC) after radiotherapy. 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 tumours. The treatment was well tolerated, with only mild local reactions reported [7].
Animal studies on thymosin-α1 in cancer treatment
Prevents the spread of cancer and improves survival rates
Thymosin-α1 (Tα1) protected the weakened immune system from tumour spread and shortened survival in preclinical cancer models. Ishitsuka et al (1983) studied mice whose immunity was weakened by chemotherapy or X-ray exposure and then exposed to B16 melanoma or L1210 leukaemia 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 retained NK cell activity and adoptive transfer studies confirmed that the protective effect was due to spleen cells containing NK cells rather than T cells. In addition, Tα1 corrected abnormal tumour cell movement caused by the chemotherapeutic drug 5-fluorouracil (5-FU). In untreated animals, 5-FU caused tumour 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].
Strengthening immunity and inhibiting tumour growth
Brief therapy with thymosin-α1 (Tα1) activated the immune system, slowed tumour growth and reduced metastasis in a mouse model of cancer. Beuth et al (2000) implanted tumours into BALB/c mice and administered Tα1 once daily for seven days at doses ranging from 0.01 to 10 μg per mouse subcutaneously, starting 24 hours after tumour 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, tumour outcomes were improved: treated mice had fewer liver and lung metastases, and primary tumours 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 mobilise host defence mechanisms, shrink tumours and limit tumour spread [9].
Enhances immune attack and prolongs survival rate
Adding thymosin-α1 (Tα1) to hyperthermic intraperitoneal chemotherapy (HIPEC) slightly improved survival and enhanced anti-tumour immunity in a colorectal 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 with 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 tumour cells, but altered the immune response towards Th1 activity. Levels of interferon-γ (IFN-γ) and 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 tumour 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-tumour immunity and increased the efficacy of oncolytic virus treatment. Liu et al (2024) investigated how oncolytic adenovirus (ADV), although capable of killing tumour cells, could sometimes induce immune suppression within the tumour. Importantly, ADV therapy pushed tumour-associated macrophages towards a tumour-promoting M2 state and attracted more regulatory T (Treg) cells, which suppress tumour-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 tumours. As a result, these immune changes restored potent anti-tumour 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) enhanced a complex treatment strategy to improve survival and reduce tumour 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 a fortnight and then twice weekly thereafter, Huaier granules (a traditional herbal medicine with anti-tumour effects) and sirolimus (an mTOR inhibitor that blocks the growth and survival of tumour cells). The treatment lasted 20 weeks. Importantly, the triple combination provided better survival, reduced tumour incidence and significantly lowered serum alpha-fetoprotein (AFP) levels, a marker of liver cancer, compared with each single drug or double combination. Immunological tests showed that Tα1 broadly enhanced the immune response, Huaier showed direct anti-tumour activity and sirolimus blocked metabolic pathways that promote tumour growth. Combining these three drugs in a " " approach allowed to attack both cancer cells and the tumour-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 weekly, 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 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 given perioperatively and XELOX chemotherapy (capecitabine plus oxaliplatin). Interestingly, the increased dosing frequency did not result in additional benefit, suggesting that twice weekly may be sufficient. In immune reconstitution 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 with 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, without consistent evidence that they are superior to the standard approach.
Disclaimer
This article has been 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 are not suggesting 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 medicine. The information contained in the text is based on available scientific research and is not intended as medical advice or to promote self-medication. The reader should consult with a qualified health professional for all health and treatment decisions.
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 randomised 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 immunological 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 randomised 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 tumour 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 tumour weight and organ colonisation 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-tumour 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 liver cancer model]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 31(6), 744-748. PMID: 26062414. https://pubmed.ncbi.nlm.nih.gov/26062414/