3463 - Radiotherapy-Boosted Thymosin Alpha-1 Based Immunotherapy: A Cutting-Edge Approach to Amplifying Immune Dynamics and Therapeutic Efficacy in Advanced Solid Tumors

02:30pm - 03:45pm PT

Hall F

Screen: 26

POSTER

Presenter(s)

Yuehong Kong, - The Second Affiliated Hospital of Soochow University, ???, Jiangsu

Y. Kong, S. Li, M. Xu, R. Chen, J. Zhang, P. Xing, and Z. LiYuan; Center for Cancer Diagnosis and Treatment, The Second Af?liated Hospital of Soochow University, Suzhou, China

Purpose/Objective(s): Radiotherapy induced lymphopenia remains a significant barrier to the long-term success of immunotherapy. Thymosin Alpha-1 (Ta-1) plays a crucial role in protecting lymphocytes from radiation-induced lymphocytopenia and enhancing T lymphocyte function. Our previous research has shown that the PRaG regimen, which includes programmed cell death protein 1(PD-1) inhibitors, hypofractionated radiotherapy (HFRT), and granulocyte-macrophage colony-stimulating factor (GM-CSF), has demonstrated clinical promise in patients with metastatic solid tumors. This study aims to assess the efficacy and safety of a novel Ta-1-based PRaG regimen in patients with advanced solid tumors, with a particular emphasis on its effects on T cell dynamics.

Materials/Methods: Patients with advanced solid tumors who had progressed after prior systemic therapy were stratified according to baseline T lymphocyte counts and received personalized Ta-1 dosing. Patients with low baseline T lymphocyte counts received a 7-day loading dose of Ta-1 before radiotherapy. Those with higher baseline counts received maintenance Ta-1(1.6 mg, thrice weekly) in combination with the PRaG regimen for at least two cycles. In each PRaG cycle, HFRT (3×8Gy or 3×5Gy) was delivered to one metastatic site, GM-CSF (200 µg) was administered subcutaneously daily for one week starting on the first day of radiotherapy, and a PD-1 inhibitor was given intravenously once within one week after completion of HFRT. The PRaG regimen was repeated every 21 days for at least two cycles. Following PRaG treatment, patients continued PD-1 inhibitors and Ta-1 until disease progression or intolerable adverse events. The primary endpoint was the objective response rate (ORR) by RECIST 1.1 criteria. Peripheral immune profiling was conducted via flow cytometry, single-cell sequencing, and T-cell receptor sequencing to assess the impact of radiotherapy and Ta-1 on T cell dynamics.

Results: Among 21 enrolled patients, the ORR was 23.8%, and the disease control rate was 47.6%. The median progression-free survival was 3.97 m(95% CI: 2.67–6.97 m), with no Grade 3 or higher adverse events reported. Immune analysis revealed significant increases in CD8⁺T cells, NK cells, and CD4⁺T_EM cells after Ta-1 loading, alongside a notable decrease in regulatory T cells(p=0.001). Single-cell sequencing identified higher clonality in GZMK⁺CD8⁺T cells and LEF1⁺Naïve CD8⁺T cells in responders, while TRDV2⁺CD8⁺T cells expanded in non-responders. These findings suggest that radiotherapy, in combination with Ta-1, may enhance immune priming, enabling the immune system to respond more effectively to treatment.

Conclusion: Integrating Ta-1 into the PRaG regimen, represents a promising advancement in the treatment of advanced solid tumors. This approach enhances immune response by protecting lymphocytes, promoting effective T cell dynamics, and offering a favorable safety profile. Further validation in larger cohorts is needed to confirm these findings.