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Updated: Jun 6, 2026
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies
Paolo A Ascierto1, Ester Simeone, Mario Sznol
1Unit of Medical Oncology and Innovative Therapy, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy. paolo.ascierto@gmail.com
Abstract:
Monoclonal antibodies (mAbs) provide a pharmacological platform to block or activate the function of surface receptors. The immune system has evolved receptor-ligand pairs that repress or empower the cellular immune response, which, if tampered with, unleash more potent cellular immunity against tumor antigens. Agonist antibodies directed against CD137 (4-1BB) on the surface of antigen-primed T lymphocytes increase tumor immunity that is curative against some transplantable murine tumors. A fully human IgG4 anti-CD137 antibody is under development with signs of clinical activity and cases of severe liver toxicity that seem to be on-target and dose-dependent effects. Programmed death-1 (PD1) is a surface molecule delivering inhibitory signals important to maintain T-cell functional silence against their cognate antigens. Interference with PD1 or its ligand PD-L1 (B7-H1) increases antitumor immunity. As a result anti-PD1 and anti-PD-L1 human mAbs are under clinical development. Phase I trials with anti-PD1 mAb have yielded encouraging results with durable objective responses and a reasonable safety profile. As new class of drugs in cancer therapy, immunostimulatory mAbs have resulted in redefinition of tumor response criteria and rethinking of the rationale for combining these among each other and with other strategies.
Insights
Immunostimulatory monoclonal antibodies (mAbs) harness the immune system to fight cancer by targeting receptors like CD137 and PD-1. These therapies show promise but require careful management due to potential toxicities.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Monoclonal antibodies (mAbs) are versatile tools for modulating immune responses by targeting cell surface receptors.
- Immune checkpoints, such as PD-1/PD-L1 and activating receptors like CD137, play critical roles in regulating T-cell activity against tumors.
Purpose of the Study:
- To review the therapeutic potential and challenges of immunostimulatory monoclonal antibodies in cancer treatment.
- To discuss the mechanisms, clinical development, and safety profiles of anti-CD137 and anti-PD-1/PD-L1 antibodies.
Main Methods:
- Review of preclinical and clinical data on immunostimulatory mAbs.
- Analysis of receptor-ligand interactions in immune regulation.
- Evaluation of clinical trial outcomes and toxicity profiles.
Main Results:
- Agonist anti-CD137 antibodies enhance anti-tumor immunity, with clinical trials showing activity but also dose-dependent liver toxicity.
- Anti-PD-1 and anti-PD-L1 antibodies demonstrate encouraging results in Phase I trials, with durable responses and manageable safety.
- These therapies are redefining cancer treatment strategies and combination approaches.
Conclusions:
- Immunostimulatory mAbs represent a significant advancement in cancer immunotherapy.
- Careful patient selection, dosing, and toxicity monitoring are crucial for optimizing treatment outcomes.
- Further research into combination strategies holds promise for improving efficacy.
