Advancing Immune Checkpoint Research in Immuno-Oncology

Immune checkpoints are critical regulators of T-cell activation and immune tolerance. Tumors exploit pathways such as PD-1/PD-L1 and CTLA-4 to suppress anti-tumor immune responses and promote immune escape.

Immune checkpoint inhibitors block these inhibitory signals to restore anti-tumor immune responses in a subset of patients and modern research now focuses on addressing: 

• T-cell exhaustion and dysfunction. 
• Resistance to existing checkpoint inhibitors. 
• Synergistic strategies through combination immunotherapy. 

Figure 1: Mechanism of PD-1/PD-L1 blockade . Left: PD-L1/PD-1 interaction inhibits T-cell activity, leading to tumor immune escape. Right: Neutralizing antibodies block this signal to restore T-cell activation and tumor cell death. 

Key Immunotherapy Targets

Overcoming Resistance: Combination & Next-Gen Strategies

Modern immunotherapy increasingly relies on combination strategies to address treatment resistance and complex tumor microenvironments (TME).

Synergistic Combination Screening 

Co-expression of inhibitory receptors such as PD-1 and LAG-3 on exhausted T cells has made dual checkpoint blockade a promising strategy for overcoming resistance to immunotherapy and restoring anti-tumor immune responses.

• PD-1:PD-L1 Cell-Based Inhibitor Screening Assay Kit
  → Evaluate checkpoint blockade activity and functional restoration of T-cell signaling.
• LAG3 / NFAT Reporter - Jurkat Recombinant Cell Line
  → Investigate LAG-3-mediated signaling and T-cell exhaustion pathways.
• Anti-LAG3 Neutralizing Antibodies
  → Characterize checkpoint blockade and modulation of LAG-3 inhibitory signaling.

Figure 2: Dual Checkpoint Targeting (LAG-3 & PD-1) . Dual blockade of the PD-1 and LAG-3 pathways on exhausted T cells to overcome resistance and trigger synergistic anti-tumor responses 

Metabolic & Myeloid Checkpoints

Emerging pathways such as IDO1, VISTA, and BTLA contribute to immune suppression within the tumor microenvironment and are increasingly explored as next-generation immuno-oncology targets.

• IDO1 Fluorogenic Inhibitor Screening Assay Kit
  → Study metabolic immunosuppression and screen inhibitors targeting the IDO1 pathway.
• B7-H5 (VISTA) Fc Fusion Protein
  → Investigate VISTA-mediated immune suppression and myeloid checkpoint signaling within the tumor microenvironment.
• Anti-VISTA Neutralizing Antibody
  → Characterize VISTA/VSIG3 checkpoint blockade and inhibitory immune signaling pathways.
• VSIG-3:VISTA Inhibitor Screening Assay Kit
  → Evaluate inhibitors targeting the VSIG-3/VISTA interaction for next-generation immunotherapy research.
• BTLA (CD272) Fc Fusion Protein
  → Explore inhibitory immune regulation and early-stage checkpoint signaling mechanisms.

Bispecific Antibody Characterization

Bispecific antibodies targeting multiple immune checkpoint pathways are emerging as promising approaches to enhance anti-tumor immune responses and overcome resistance mechanisms.

• CTLA4:B7-1 TR-FRET Assay Kit 
  → Characterize checkpoint ligand-receptor interactions and evaluate inhibitory pathway modulation.
• TIGIT:CD155 Homogeneous Assay Kit 
  → Study TIGIT/CD155 checkpoint interactions and evaluate combination immunotherapy strategies.
• FGL1:LAG3 TR-FRET Assay Kit 
  →  Evaluate inhibitors and bispecific approaches targeting the FGL1/LAG-3 immune checkpoint axis.

Navigating the Complexity of the Tumor Microenvironment

The diversity of co-inhibitory pathways within the tumor microenvironment (TME) requires a structured approach to drug discovery. To support your immunotherapy projects from initial target identification to advanced cellular validation, Tebubio provides a comprehensive, three-phase research workflow.

Phase 1: Interaction Screening

Identify checkpoint ligand-receptor interactions and screen blocking candidates using biochemical and TR-FRET assays.

• PD-1:PD-L1 Inhibitor Screening Assay Kit 
• TIGIT:CD155 Homogeneous Assay Kit 
• CTLA4:B7-1 TR-FRET Assay Kit 
• FGL1:LAG3 TR-FRET Assay Kit 

Figure 3: Key Inhibitory Pathways in the Tumor Microenvironment. Overview of major receptor-ligand interactions. These pathways represent the primary targets for interaction screening, functional assays, and next-gen combinations.  

Phase 2: Functional Blockade & Signaling

Evaluate checkpoint blockade activity and restoration of T-cell signaling using reporter systems and cell-based bioassays.

• PD-1/PD-L1 Cell-Based Assay Kit 
• LAG-3/NFAT Reporter Jurkat Cell Line

Phase 3: Cell Engineering & Translational Models

Integrate checkpoint modulation into advanced CAR-T/NK and translational immunotherapy workflows.

• PD-L1 Lentivirus
  → Stable checkpoint overexpression models.  
• PD-1 CRISPR/Cas9 Lentivirus, Integrating 
  → For stable PD-1 gene editing models. 
• PD-1 CRISPR/Cas9 Lentivirus, Non-Integrating 
  → For transient gene editing approaches and reduced integration-related concerns.
• Recombinant Proteins
  → High-purity checkpoint proteins for ligand binding and functional immuno-oncology assays.
• Co-culture Checkpoint Models: Utilizing ligand-expressing target cells and neutralizing antibodies to mimic the tumor microenvironment.

Complete Your Immunotherapy Workflow

Beyond target cell models, Tebubio provides complementary solutions to support every stage of your CAR-T and CAR-NK development pipeline:

• → Custom Target Cell Line Engineering: Tailored target expression and reporter systems. 
• → Effector Cells: Pre-validated, cryopreserved CAR T (CAR NK upon request) cells. 
• → Functional Assays: Reporter-based cytotoxicity, immune activation, and potency assays.
• → Scientific & Technical Support: Guidance on target selection and assay optimization.

• Ready-to-use cryopreserved CAR-T cells for rapid functional studies
• 100+ CAR constructs available (DNA, mRNA, LNP, or engineered cells)

mRNA-LNP delivery :

• No cloning. No viral packaging. Fast, streamlined workflows
• 78–99% transfection efficiency in primary T, NK, iPSC, and dendritic cells

• Integrated functional assays, including real-time killing, binding, and cytokine analysis
• Clinically validated technology, supported by 20+ patents and 4 clinical-stage programs (up to Phase II)

Need Support for Your Checkpoint Research?

Whether you are developing checkpoint inhibitors, engineered immune therapies, or translational immuno-oncology assays, Tebubio helps accelerate your research with validated solutions and scientific support.

• References

  Article content created by Tebubio using courtesy materials provided by BPS Bioscience.

  Figures from articles:

  • Figure 1: Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets — MDPI | Journals | Cancers | Volume 12 | Issue 7
  • Figure 2: LAG3 as a Cotherapy for Immune Checkpoints — by BPS Bioscience.
  • Figure 3: Immune Checkpoint Molecules — by BPS Bioscience.