Thymosin Alpha-1

Gender influences clinical presentations, duration and severity of symptoms, and therapy outcome in coronavirus disease 2019 (COVID-19) infection. Whether the immune response to Tα1 treatment for SARS-CoV-2 differs between the sexes, and whether this difference explains the male susceptibility to COVID-19, is unclear. This study aimed to investigate the efficiency and safety of Tα1 treatment and provide a basis for practically identifying gender differences characteristics and features of COVID-19. One hundred twenty-seven patients had COVID-19 symptoms and tested COVID19-positive (female 42.52%) in Wuhan union hospital were enrolled for medication. They were randomly divided into groups Control and Tα1 intervention. Seventy-eight patients received a subcutaneous injection of 1.6 mg Tα1, based on supportive treatment for 15 days. The control group included untreated 49 COVID19 patients closely matched for gender and age and received regular supportive treatment. In this retrospective analysis, we found that COVID-19-infected males reported more symptoms than COVID-19-infected females. A high degree of gender differences-related variability was observed in CRP and PCT levels and the cell counts of many lymphocyte subpopulations in the COVID-19 patients after Tα1 intervention. Levels of CRP and IL-6 were higher in Tα1-treated male group than Tα1-treated female group, while the level of PCT was significantly lower in Tα1-treated male group. Gender differences may be a factor in sustaining COVID-19 immunity responded to Tα1, male and female show statistically significant differences in relevance to cytokine production associated with the development of a more significant number of symptoms. This leaves the question of identifying gender-specific risk factors to explain these differences.

To validate the efficacy and safety of thymosin α-1 combined with lenvatinib plus sintilimab in the treatment of unresectable hepatocellular carcinoma. Patients with unresectable hepatocellular carcinoma treated with lenvatinib plus sintilimab at the People's Hospital of Guangxi Zhuang Autonomous Region from January 2020 to June 2022 were retrospectively analyzed. The patients were divided into an experimental group and a control group based on their therapeutic regimens: thymosin α-1 plus lenvatinib and sintilimab (experimental group), and lenvatinib plus sintilimab (control group). The primary endpoints were overall survival and progression-free survival. Tumor response was evaluated according to mRECIST criteria, and the partial response, complete response, stable disease, progressive disease, object response rate, and disease control rate of the two groups were compared. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events version 5.0. The median overall survival of all patients was 13.0 months (95% CI 10.587-15.413). The experimental group had a longer median overall survival than the control group (16 months vs. 11 months, P = 0.018). The median progression free survival of all patients was 5.0 months (95% CI 3.721-6.279). The experimental group had a longer median progression-free survival than the control group (7 months vs. 4 months, P = 0.006). The objective response rate of the experimental group was 55.8% (24/43), and of the control group's 34.7% (17/49) (P = 0.042). The disease control rate of the experimental group was 76.7% (33/43), while the control group had a rate of 59.2% (29/49) (P = 0.073). There was no significant difference in the incidence of grade 1-2 adverse events or grade 3-4 adverse events between the two groups (P > 0.05). Thymosin α-1 combined with lenvatinib plus sintilimab is an effective and safe therapeutic regimen in unresectable hepatocellular carcinoma.

RATIONALE: Triple-negative breast cancer is characterized by a worse prognosis compared with other breast cancer subtypes, especially in the case of pretreated metastatic triple-negative breast cancer (mTNBC). Because of the limited treatment options and suboptimal response rates, there is a pressing need to explore novel treatment protocols. PATIENT CONCERNS: A 48-year-old female patient diagnosed with mTNBC who had not responded to multiple lines of therapy (including surgery, chemotherapy, and radiotherapy) but demonstrated significant efficacy and abscopal effects after enrolling in our clinical trial. DIAGNOSES: Triple-negative breast cancer with lung metastases. INTERVENTIONS: The clinical trial combined stereotactic body radiotherapy, immunotherapy, granulocyte-macrophage colony-stimulating factor, and thymosin alpha-1 to treat previously treated metastatic solid cancers. OUTCOMES: This combined treatment regimen implemented in this clinical trial yielded the patient's notable efficacy, accompanied by abscopal effects. The target lesion and the 3 observed lesions achieved a partial response according to the RECIST v1.1 criteria. reevaluation scans after 2 cycles of immunotherapy indicated a regression rate of -78.97% for the target lesion and -56.73% for the observed lesions. Hematological indexes were stable, and there was no apparent myelosuppression. Also, the tumor marker CA-199 exhibited a downward trend. During the course of treatment, the patient experienced a grade 2 skin reaction, which improved after receiving antiallergic treatment. No further adverse effects were observed. LESSONS: This treatment regimen may offer a promising treatment strategy for patients with mTNBC and other metastatic solid cancers.

T alpha 1, a 28-amino-acid peptide, is derived from PT alpha, which is an intracellular, nonsecretory protein of unknown function. Both T alpha 1 and PT alpha are found in the blood of normal individuals. Subcutaneous and intramuscular injections of T alpha 1 in doses up to 9.6 mg/m2 are tolerated without side effects, and 0.9 mg/m2 injections raise the serum level approximately 30-fold after 1 hr of administration, which slowly returns to baseline within 24 hr. In vitro, and perhaps in vivo, T alpha 1 restores normal T-cell function. It increases IL-2 production and IL-2 receptors in normal mitogen-stimulated T cells and stimulates IL-3 production in immunocompromised mice. The dose-response relationship for these effects is not linear and may be bimodal. T alpha 1 binds to VIP receptors and inhibits in vitro and xenograft growth of non-SCLC cell lines. In patients with nonbulky carcinomas who have received standard therapy, T alpha 1 is possibly effective in prolonging the time to relapse and in improving survival. At present there is a great need to clearly define the clinical role of T alpha 1 in cancer patients. A major problem encountered in studies with T alpha 1 will, however, be the present lack of knowledge with regard to its mechanism in effecting tumor growth. It is not at all clear whether its immunomodulatory functions, its interaction with VIP receptors, or none of these mechanisms are related to its antineoplastic activities. In addition, the apparent nonlinear dose-response relationship will make it difficult to choose a reasonable dosing schedule for clinical trials. This is particularly apparent in light of the experimental animal data summarized above where a tumor response was seen at doses of 4 micrograms/kg and 400 micrograms/kg but not at 0.4 microgram/kg and 40 micrograms/kg. This dose range could conceivably be given to humans since 9.6 mg/m2, the maximum dose given to humans without major side effects to date, is roughly equivalent to 250 micrograms/kg. At this time a reasonable clinical approach would be a well-designed risk factor stratified phase III clinical trial using 0.9 mg/m2 T alpha 1 subcutaneously twice a week compared to a control group to substantiate the data reported by Schulof et al. Before such data are available, T alpha 1 should not be used in clinical oncology.

This study investigated the anti-tumor effects of stereotactic body radiation therapy (SBRT) with thymosin alpha-1 (Tα1) in heavily pretreated, metastatic esophageal squamous cell carcinoma (mESCC) patients. Thirty-one patients with at least 2 metastatic sites were enrolled. SBRT was delivered with a daily fraction of 5.0 Gy for a total dosage of 25 Gy over one week to one metastatic lesion. Concurrent Tα1 (1.6mg subcutaneously) was administered twice a week with an interval of 3-4 days until tumor progression of other documented metastatic lesions. Anti-tumor effects (the primary endpoint) were evaluated by assessing the CT/MRI response of other distinct measurable lesions. Secondary endpoints included treatment safety, survival outcomes and immune-related blood parameters. This study was registered at ClinicalTrials.gov (NCT 02545751). Partial response occurred in three (9.7%) patients, and 11 (35.5%) patients had stable metastatic disease, which yielded a metastatic-lesion control rate of 45.2%. Seventeen (54.8%) patients were documented to have progressive disease in other metastatic lesions. The median overall survival and abscopal progression free survival (APFS) times were 5.2 and 2.9 months, respectively. Significant differences in survival outcomes were observed between the abscopal control group (without progression in the abscopal lesions at 12 weeks) and the non-control group (P = 0.035 and 0.044, respectively). Treatment-related toxicity was acceptable, and no grade 4 acute toxicity occurred. Immunomonitoring of lymphocytes showed that the proportion of CD8+ T cells after treatment was significantly different between the abscopal control group and the non-control group (P=0.047). In conclusion, the combination of SBRT with Tα1 produced encouraging effects in heavily pretreated, mESCC patients and further research on radiation enhanced immunotherapy is warranted.

This study was conducted to determine whether the adding thymosin alpha-1 to standard of care for re-treatment of nonresponding hepatitis C infections can improve sustained viral response (SVR) rates. Patients (n = 552) with hepatitis C infections not responding to the combination of Peginterferon alfa-2a or 2b with ribavirin (RBV)were randomized to receive peginterferon alfa-2a 180 mg/week with RBV 800-1200 mg/daily plus either thymosin alpha-1 1.6 mg SC twice weekly (n = 275) or placebo (n = 277) for 48 weeks. Eighty-eight per cent of patients had HCV genotype 1, 6.6% type 4, 2.2% type 2 and 3.6% type 3. SVR rates in the intention to treat population were similar between thymosin alpha-1 and placebo (12.7%vs 10.5%; P = 0.407). Among patients who completed all 48 weeks of therapy, the SVR rate was significantly higher in the thymosin alpha-1 group at 41.0% (34/83) compared with 26.3% (26/99) in the placebo group (P = 0.048). No significant difference was observed between treatment groups in the incidence of adverse events. The addition of thymosin alpha-1 to the standard of care did not increase the on-treatment HCV viral response. Thymosin alpha-1 seems to play no role in the primary therapy of the disease. This study raises the hypothesis that thymosin alpha-1 may have a secondary therapeutic role as an adjuvant in the prevention of relapses in patients achieving a virologic response during therapy.