Recombinant tumor necrosis factor-thymosin-α1 in combination with polychemotherapy in a patient with pancreatic cancer (case report)

Background. Despite advances in recent years, treatment outcomes for pancreatic cancer remain modest. The search for ways to overcome the immune resistance of pancreatic cancer and the need to optimize treatment strategies have drawn attention to the potential combined use of chemotherapy and the cytokine gene therapy drug tumor necrosis factor-thymosin-α1 recombinant.

Оbjective. To evaluate the efficacy and safety of therapy with tumor necrosis factor-thymosin-α1 recombinant in a patient with pancreatic cancer undergoing chemotherapy.

Material and methods. Patient I., 52, presented to the clinic in August 2025 for stage III cT4N1M0 pancreatic cancer. A percutaneous biopsy of the pancreatic tumor was performed (August 5, 2025). The diagnosis was confirmed histologically, revealing ductal adenocarcinoma, G3. According to the immunohistochemistry study of August 15, 2025: BRCA1 wt, BRCA2 wt, PALB2 wt. The oncology board prescribed courses of chemotherapy with the FOLFIRINOX regimen. To reduce the likelihood and severity of undesirable side effects associated with chemotherapy, the patient sought simultaneous cytokine gene therapy. The patient's condition was monitored using the Karnofsky status, CEA, CA19-9, and tumor necrosis factor-alpha levels. Computed tomography with intravenous contrast was used to assess the tumor response to treatment according to RECIST 1.1 criteria.

Results. The patient was prescribed cytokine gene therapy with tumor necrosis factor-thymosin-α1 recombinant (rTNF-α1) according to the regimen developed at the clinic. During combination therapy, the patient noted a gradual improvement in his overall well-being, a decrease in pain severity, and was able to not only perform feasible housework but also partially return to his professional activities. Treatment toxicity associated with the use of chemotherapy did not exceed grades 1-2 according to CTCAE 5.0 (nausea and grade 1-2 leukopenia). No additional side effects associated with the use of rTNF-α1 were noted. When assessing the tumor process according to RECIST 1.1 criteria, after 5 courses of cytokine gene therapy and 9 courses of chemotherapy, a partial response was achieved, a decrease in target lesions by 36,9% from the initial level was noted. The patient currently continues to receive combination therapy with rTNF-α1 and chemotherapy. The patient's survival from diagnosis is 7+ months.

Conclusion. Further clinical studies are needed to determine the role of combination therapy with tumor necrosis factor-thymosin-α1 recombinant and chemotherapy in patients with pancreatic cancer.

1. Mannucci A., Goel A. Advances in pancreatic cancer early diagnosis, prevention, and treatment: The past, the present, and the future. СА: А Cancer J for Clinicians. 2026; 76 (Issue1): e70035. https://doi.org/10.3322/caac.70035.

2. Strobel O., Neoptolemos J., Jager D., et al. Optimizing the outcomes of pancreatic cancer surgery. Nat Rev Clin Oncol. 2019; 16 (1): 11-26. https://doi.org/10.1038/s41571-018-0112-1.

3. Dasari A., Shen C., Halperin D., et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017; 3 (10): 1335-1342. https://doi.org/10.1001/jamaoncol.2017.0589.

4. Yamada D., Kobayashi S., Takahashi H., et al. Results of a randomized clinical study of gemcitabine plus nab-paclitaxel versus gemcitabine plus S-1 as neoadjuvant chemotherapy for resectable and borderline resectable pancreatic ductal adenocarcinoma (RCT, CSGO-HBP-015). Ann Surg Oncol. 2024; 31 (7): 4621-4633. https://doi.org/10.1245/s10434-024-15199-8.

5. Kim I. K., Diamond M. S., Yuan S., et al. Plasticity-induced repression of Irf6 underlies acquired resistance to cancer immunotherapy in pancreatic ductal adenocarcinoma. Nat Commun. 2024; 15 (1): 1532. https://doi.org/10.1038/s41467-024-46048-7.

6. Wainberg Z. A., Hochster H. S., Kim E. J., et al. Open-label, phase I study of nivolumab combined with nab-paclitaxel plus gemcitabine in advanced pancreatic cancer. Clin Cancer Res. 2020; 26 (18): 4814-4822. https://doi.org/10.1158/1078-0432.ccr-20-0099.

7. Ilyushin A. L., Ben Ammar A. M. A case of successful treatment of pancreatic cancer. Rossiiskii onkologicheskii zhurnal. 2022; 27 (5): 243-250. (In Russ.) https://doi.org/10.17816/onco456482

8. Solmonese L., Lofiego M. F., Fazio C., et al. The Immunomodulatory Activity of Thymosin Alpha 1 on Tumor Cell Lines and Distinct Immune Cell Subsets. Onco Targets Ther. 2025; 18: 995-1012. https://doi.org/10.2147/OTT.S527785.

9. Wei Y. T., Wang X.-R., Yan C., et al. Thymosin α-1 reverses M2 polarization of tumor-associated macrophages during efferocytosis. Cancer Res. 2022; 82 (10): 1991-2002. https://doi.org/10.1158/0008-5472.CAN-21-4260.

10. Nevo N., Lee Goldstein A., Bar-David S., et al. Thymosin alpha 1 as an adjuvant to hyperthermic intraper-itoneal chemotherapy in an experimental model of peritoneal metastases from colonic carcinoma. Int Immunopharmacol. 2022; 111: 109166. https://doi.org/10.1016/j.intimp.2022.109166.

11. Yao S., Huang Q., Zou Y., et al. The efficacy and safety of thymosin alpha-1 combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma: a retrospective study. Sci Rep. 2025, 15: 13960. https://doi.org/10.1038/s41598-025-97160-7.

12. Danielli R., Cisternino F., Giannarelli D., et al. Long-term follow up of metastatic melanoma patients treated with Thymosin alpha-1: Investigating immune checkpoints synergy. Expert Opin Biol Ther. 2018; 18 (sup. 1): 77-83. https://doi.org/10.1080/14712598.2018.

13. Guo C.-L., Mei J.-D., Jia Y.-L., et al. Impact of thymosin α1 as an immunomodulatory therapy on long-term survival of non-small cell lung cancer patients after R0 resection: a propensity score-matched analysis. Chin Med J (Engl). 2021; 134 (22): 2700-2709. https://doi.org/10.1097/CM9.0000000000001819.

14. Sha L., Zhang H., Zhang X. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery. Open Life Sci. 2024; 19 (1): 20220793. https://doi.org/10.1515/biol-2022-0793.

15. Mercogliano M. F., Bruni S., Mauro F., et al. Harnessing Tumor Necrosis Factor Alpha to Achieve Effective Cancer Immunotherapy. Cancers. 2021; 13 (3): 564. https://doi.org/10.3390/cancers13030564.

16. Ilyushin A. L., Krasnaya Ya. L., Shabalkin P. I. The results of an open comparative study in parallel groups of the efficacy and safety of the Refnot® (tumor necrosis factor thymosin 1 alpha recombinant) drug in the treatment of disseminated triple negative breast cancer. Meditsina. 2019, 7(3): 138-149. (In Russ.) https://doi.org/10.29234/2308-9113-2019-7-3-138-149.