Adding the Immune Peptide Thymosin-α1 to Radiation and Immunotherapy Shrank Distant Tumors in Nearly 1 in 4 Patients | Research

The takeaway

A four-part treatment combining radiation, PD-1 immunotherapy, GM-CSF, and the peptide thymosin-α1 achieved a 65% disease control rate in heavily treated cancer patients, with nearly a quarter showing shrinkage of tumors far from the radiation site.

23% abscopal effects
of heavily pretreated metastatic cancer patients showed tumor shrinkage at distant sites not directly irradiated — suggesting systemic immune activation

What the researchers found

In this Phase II trial, combining hypofractionated radiotherapy with PD-1 inhibitor immunotherapy, GM-CSF, and the peptide thymosin-α1 achieved a 23.08% objective response rate and 65.38% disease control rate in heavily pretreated metastatic cancer patients. Median progression-free survival was 3.5 months. Notably, abscopal effects (tumor shrinkage at sites not directly irradiated) were observed in 23.08% of patients, with four achieving partial responses. Lower baseline neutrophil-to-lymphocyte ratio predicted better outcomes. The regimen was manageable with six grade 3-4 adverse events and no treatment-related deaths.

Why it matters

Patients with heavily treated metastatic solid tumors have few remaining options. This trial demonstrates that adding the immunomodulatory peptide thymosin-α1 to a radiation-immunotherapy combination can produce meaningful responses including abscopal effects — where distant tumors shrink from local radiation combined with systemic immune activation. This suggests thymosin-α1 enhances the immune priming effect.

The numbers in context

n=37 · 23.08% ORR · 65.38% DCR · median PFS 3.5 months · 23.08% abscopal effects · 6 grade 3-4 AEs · 0 grade 5 AEs · median follow-up 5.97 months

How the study worked

Multicenter Phase II trial enrolling patients with heavily treated metastatic solid tumors from September 2022 to May 2024. Treatment: HFRT to targeted tumors + GM-CSF for 14 days from day 1 + thymosin-α1 twice weekly until progression + camrelizumab (PD-1 inhibitor) every 3 weeks after HFRT. Endpoints included PFS, ORR, DCR, abscopal effects, and safety. Analysis by intention-to-treat.

Who was studied

37 adults with heavily pretreated metastatic solid tumors across multiple cancer types

What this study cannot tell us

Small sample size (37 patients) in a single-arm Phase II trial without a control group. Overall survival data not yet mature. Median follow-up of only 5.97 months is short. Cannot determine the individual contribution of thymosin-α1 versus the other components. Heterogeneous tumor types may complicate interpretation.

How to read the evidence

This is a multicenter Phase II clinical trial with human patients, representing moderate-quality clinical evidence. However, it is single-arm (no control group), has a small sample size (37 patients), and overall survival data is immature, limiting definitive conclusions.

When this study was published

Published in 2025 with enrollment through May 2024. This is current clinical research reflecting the modern trend of combining immunotherapy with radiation and immune-modulating peptides.

The bigger picture

The combination of radiation with immunotherapy to generate systemic anti-cancer immune responses (the abscopal effect) has been a long-sought goal in oncology. Adding thymosin-α1 to this mix may enhance immune priming — the peptide has a long history as an immune modulator and is approved in several countries. This trial adds to growing evidence that peptide-based immune modulators can meaningfully augment cancer immunotherapy strategies.

Questions still open

What is the specific contribution of thymosin-α1 to the abscopal effect — would the same results occur without it?
Which cancer types respond best to this combination, and could biomarkers like neutrophil-to-lymphocyte ratio guide patient selection?
Would a larger randomized Phase III trial confirm these promising results?

Common questions

What is thymosin-α1 and how does it help fight cancer?

Thymosin-α1 is a 28-amino acid peptide naturally found in the thymus gland that plays a key role in training immune cells. As a drug, it boosts the maturation and activity of T cells and other immune cells. In this trial, it was used alongside radiation and immunotherapy to enhance the body's immune response against cancer cells.

What is the abscopal effect and why is it significant?

The abscopal effect occurs when radiation to one tumor causes distant, unirradiated tumors to shrink. This happens because radiation can release tumor antigens that, combined with immune-stimulating treatments like thymosin-α1 and PD-1 inhibitors, train the immune system to recognize and attack cancer cells throughout the body — essentially turning a local treatment into a systemic one.

Read the original research

Hypofractionated radiotherapy combined with a 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 : CII, 74(3), 98

View on PubMed ↗Publisher’s paper ↗

Citation

Yu, Jiamin; Yin, Li; Guo, Wenjie; Wang, Qiang; Liu, Juying; Zhang, Lansheng; Ye, Hongxun; Xia, Jianhong; Xia, Youyou; Wu, Jianfeng; Wang, Wanwei; Yang, Yanguang; Zong, Dan; He, Xia; Wang, Lijun; Jiang, Hong. (2025). Hypofractionated radiotherapy combined with a 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 : CII, 74(3), 98. https://doi.org/10.1007/s00262-024-03934-9