Emerging targets for anticancer vaccination: PD-1
J Tobias1, P Steinberger2, M Drinić1
1Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
Abstract:
Among the mechanisms by which tumor cells escape the immune surveillance, one is the interaction between programmed cell death protein 1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1). Inhibition of the PD-1/PD-L1 pathway with monoclonal antibodies as immune checkpoint inhibitors targeting PD-1 or its ligand, PD-L1, represents a milestone in cancer therapy. The application of these antibodies, however, suffers from drawbacks including failure to show a response or benefit in a majority of patients following monotherapy or combination therapy, their frequent administration, and cost intensiveness. Small peptides capable of interfering with PD-1/PD-L1 interaction represent interesting alternatives to antibody-based immune checkpoint inhibitors. Moreover, peptides representing PD-1 or PD-L1 sequences can be used in active immunization approaches to induce antibodies that enhance antitumor immunity by effectively preventing PD-1-mediated inhibition in the host. Importantly, such peptides can readily be combined with peptides derived from cancer antigens to effectively induce an antitumor immune response. In this review, we have summarized the recent developments in the use of small molecules and peptides either to directly block PD-1/PD-L1 interaction, or in vaccination approaches to induce antibody responses stimulating anticancer immunity by blocking PD-1-mediated T-cell inhibition.
Insights
Small peptides offer a promising alternative to antibody-based immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway. These peptides can block tumor immune evasion and be used in vaccines to boost anti-cancer immunity.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Tumor cells evade immune surveillance partly through the programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) interaction.
- Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway with monoclonal antibodies have advanced cancer therapy but face limitations such as limited efficacy, frequent administration, and high costs.
Purpose of the Study:
- To review recent developments in using small molecules and peptides to overcome limitations of current PD-1/PD-L1 pathway inhibitors.
- To explore peptide-based strategies for blocking PD-1/PD-L1 interactions and for active immunization to enhance anti-tumor immunity.
Main Methods:
- Review of literature on small molecules and peptides targeting the PD-1/PD-L1 pathway.
- Analysis of peptide-based active immunization strategies for cancer therapy.
Main Results:
- Small peptides can directly interfere with PD-1/PD-L1 interactions, offering an alternative to antibodies.
- Peptides derived from PD-1 or PD-L1 sequences can be used in vaccination approaches to induce antibodies that block PD-1-mediated T-cell inhibition.
- Combining cancer antigen peptides with PD-1/PD-L1 blocking peptides can enhance anti-tumor immune responses.
Conclusions:
- Small molecules and peptides represent promising alternatives to antibody-based ICIs for cancer treatment.
- Peptide-based vaccines hold potential for inducing robust anti-tumor immunity by modulating the PD-1/PD-L1 pathway.
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