Zadaxin (thymalfasin)

This commentary emphasizes that distinguishing between population replacement and cellular rejuvenation is paramount for predicting long-term durability. Future clinical translations should look beyond the CD8+ compartment to integrate the pleiotropic effects of these agents on the broader immune landscape to ensure both oncological efficacy and systemic immunological safety.

This regimen employs short-course stereotactic body radiotherapy (SBRT, 24Gy/3Fx) as the radiotherapy component, combined with cadonilimab (a PD-1/CTLA-4 bispecific antibody), GM-CSF and thymosin α1 to form the PRaG5.0, alongside chemotherapy with nab-paclitaxel...The patient's progression-free survival (PFS) now exceeds 12 months. This case indicates that for massive, refractory cervical tumors, PRaG5.0 combined with chemotherapy followed by sequential chemoimmunotherapy may offer an effective approach for controlling disease and extending survival.

Improvements in FACT-L scores were most evident in Group-A (P< 0.05), and declines in 6MWD were smallest in this group(P< 0.05). Thymalfasin combined with ICIs and chemotherapy, particularly platinum-based doublet regimens, may significantly prolong survival, enhance immune function, and improve quality of life in patients with advanced NSCLC, without increasing treatment-related toxicity.

Combined IL-15 and Tα1 therapy reverses CD8+ T cell senescence and enhances antitumor immunity in HCC through suppression of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.

P2, N=30, Recruiting, Zekuan Xu | Trial primary completion date: May 2025 --> Jan 2026

Neoadjuvant serplulimab, SOX, and thymalfasin produced encouraging pathological response, substantial nodal clearance, and an acceptable safety profile in stage III G/EGJ adenocarcinoma. Peripheral immune and transcriptomic profiling are consistent with a hypothesis in which thymalfasin may help preserve and coordinate systemic antitumor immunity without excessive toxicity. These findings warrant further larger randomized trials.

P=N/A, N=300, Not yet recruiting, Nanjing Medical University

Complementary transcriptomic analysis using a compact four-gene Tα1 Response Index (Tα1-RI: TLR9, TLR2, IRF1, NLRC5) in TCGA-BRCA (n = 1,112) confirmed positive correlations with antigen presentation and cytotoxic programs and enrichment in CD8-like T cells in single-cell datasets. Collectively, these findings demonstrate that Tα1 enhances CD8+ T cell cytotoxicity while alleviating exhaustion, supporting its potential as an adjunct immunomodulator for improving immune surveillance in breast cancer.

P2, N=48, Recruiting, The First Affiliated Hospital with Nanjing Medical University

It represents a promising therapeutic approach to counteract age-related immune dysfunction and inflammation, potentially by slowing the aging process. Further research is needed to validate its long-term efficacy and safety in geriatrics.

The incidence of adverse events was lower in the experimental group (50.8% vs 65.8%; χ2 = 8.35, p = 0.004), primarily due to a reduced rate of myelosuppression. The addition of Tα1 to PD-1/PD-L1 inhibitor-based chemotherapy may enhance treatment efficacy, improve immune response, and reduce immunosuppression-related toxicity in patients with platinum-resistant recurrent ovarian cancer.

It should be noted that the median follow-up of 13.7 months may be insufficient to fully assess long-term survival outcomes and the potential for late-onset toxicities. As this was an exploratory analysis across multiple tumor types, these findings warrant validation in larger, randomized studies with more homogenous cohorts.