【IF 14.1】Dual-checkpoint blockade plus radiotherapy shatters the tumor-therapy ceiling! Absin ELISA kits power the “cold-to-hot” switch and abscopal-effect discovery

In oncology, converting immune-excluded “cold” tumors into inflamed “hot” tumors to ignite systemic anti-tumor immunity and eradicate metastases remains a central challenge. A 2025 Advanced Science paper entitled “Bispecific Antibody Targeting VEGF/TGF-β Synergizes with Local Radiotherapy: Turning Tumors from Cold to Inflamed and Amplifying Abscopal Effects” provides an innovative solution: the VEGF/TGF-β bispecific antibody Y332D cooperates with focal radiotherapy (RT) to re-sculpt the tumor microenvironment (TME) and markedly potentiate abscopal responses, offering a new strategy for solid tumors and their metastases. Absin’s mouse CXCL10/IP-10 ELISA kit (cat.# abs520013) supplied the accurate mechanistic data underpinning this work.

I. Background: The “Double-Edged Sword” of Radiotherapy & Rationale for the Bispecific Approach

Focal RT is a front-line modality for solid tumors. Beyond direct DNA double-strand breaks, RT can initiate an immunostimulatory cascade—cGAS-STING activation, immunogenic cell death (ICD), enhanced antigen presentation, and subsequent T-cell priming—thereby theoretically converting a cold tumor into a hot one.

 

However, RT also elicits compensatory up-regulation of VEGF (vascular endothelial growth factor) and TGF-β (transforming growth factor-β) in the TME:

· VEGF drives aberrant angiogenesis, promoting hypoxia and acidosis that suppress cytotoxic T lymphocyte (CTL) activity and dendritic cell (DC) maturation;
· TGF-β induces epithelial-mesenchymal transition (EMT), activates cancer-associated fibroblasts (CAFs), and recruits immunosuppressive cells (T_reg, M2 macrophages), counteracting RT-induced immunity and fostering radioresistance and metastasis.

Therefore, the authors hypothesized that simultaneous blockade of VEGF and TGF-β signaling would neutralize these adverse effects while amplifying RT-mediated immunostimulation.

 

II. Key Findings: Triple Synergistic Effects of Y332D + RT

Using murine 4T1 breast, CT26 colorectal, H22 hepatocellular, and GL261 glioblastoma models, the team demonstrated three mechanistically distinct but inter-locking benefits:

1. Neutralization of RT-Induced Immunosuppression & Enhanced Radiosensitivity

RT elevated VEGF and TGF-β in both tumors and plasma. Y332D dual blockade:

· Inhibited TGF-β–mediated DNA-damage repair (DDR), reducing γ-H2AX foci and tumor-cell radioresistance;

· Normalized VEGF-driven aberrant vasculature: CD31 staining showed reduced micro-vessel density (MVD) and improved oxygenation;

· Suppressed EMT and CAF activation: IHC revealed down-regulation of N-cadherin, Vimentin, and α-SMA, decreasing stromal barriers.

2. Amplification of RT-Induced Immunity: Cold → Hot Conversion

Y332D not only neutralized RT’s negative cues but also boosted its immunostimulatory capacity:

· Promoted DC maturation (CD86⁺) and M1 macrophage polarization (elevated M1/M2 ratio) by flow cytometry;

· Enhanced T-cell infiltration and functionality: increased intratumoral CD3⁺ and CD8⁺ T cells (activated CD25⁺/CD69⁺ and cytolytic GzmB⁺ subsets) and elevated CD8⁺/T_reg ratio;

· Activated type-I IFN signaling and chemokine secretion. Absin’s Mouse CXCL10/IP-10 ELISA Kit (abs520013) quantified CXCL10—an IFN-inducible chemokine recruiting CXCR3⁺ T cells—demonstrating significant up-regulation at both mRNA and protein levels, providing the chemotactic evidence for T-cell trafficking.

3. Elicitation of Abscopal Effects & Metastasis Control

The abscopal effect—regression of non-irradiated metastases via systemic anti-tumor immunity—was evaluated in the 4T1 breast lung-metastasis model:

· RT alone failed to suppress lung metastases, whereas Y332D + RT markedly reduced bioluminescent signals;

· Mechanistically, the combination augmented CD8⁺ T-cell and NK-cell infiltration/activation while decreasing myeloid-derived suppressor cells (MDSCs) in metastatic lungs, providing a cellular explanation for the abscopal response.

III. abs520013: The “Key Tool” for Chemotaxis Validation

To link IFN signaling to immune-cell recruitment, the authors quantified CXCL10 in:

1. In-vitro tumor-cell supernatants—4T1, CT26, H22, GL261 cells post-RT;
2. In-vivo tumor homogenates—confirming CXCL10 up-regulation within the TME after Y332D + RT.

Absin’s high-specificity, high-sensitivity ELISA kit provided the quantitative bridge between pathway activation and T-cell infiltration.

Kit advantages:

· Murine CXCL10-specific antibodies—no cross-reactivity;
· pg-level LLoQ—captures subtle RT-induced changes;
· 96-well format—ideal for multi-model, multi-time-point studies.

 

IV. Significance & Future Directions

This study establishes a “bispecific + RT” paradigm that simultaneously cuts immunosuppressive signaling and amplifies immunostimulatory cues, converting local therapy into systemic anti-tumor immunity against metastatic disease.

 

Absin continues to support such breakthroughs with high-precision reagents. Beyond abs520013, our portfolio covers ELISAs for IFN-β, TGF-β, VEGF, flow-cytometry antibodies, and integrated tumor-immunology solutions.

 

Reference:
Bispecific Antibody Targeting VEGF/TGF‐β Synergizes with Local Radiotherapy: Turning Tumors from Cold to Inflamed and Amplifying Abscopal Effects. Adv Sci (Weinh). 2025 Jun 5.

 

Product Used

Cat.#	Product Name	Application
abs520013	Mouse CXCL10/IP-10/CRG-2 ELISA Kit	Quantify CXCL10 in serum, plasma, and cell-culture supernatants

 

More ELISA Kits

Cat.#	Name	Publications
abs520010	Mouse TNF-α ELISA Kit	92
abs520004	Mouse IL-6 ELISA Kit	86
abs520001	Mouse IL-1β ELISA Kit	81
abs510006	Human TNF-α ELISA Kit	52
abs510003	Human IL-6 ELISA Kit	34
abs520007	Mouse IFN-γ ELISA Kit	32
abs510007	Human IFN-γ ELISA Kit	22
abs520005	Mouse IL-10 ELISA Kit	21
abs510002	Human IL-1β ELISA Kit	16
abs510005	Human IL-10 ELISA Kit	15
abs520003	Mouse IL-4 ELISA Kit	15

 

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