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Peptide Vaccines Bring New Hope to Cancer Patients

Malignant tumors are a major disease that seriously threatens human life and health. Its incidence rate is still on the rise, and the treatment methods such as surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy are constantly updated. In recent years, immunotherapy has been considered the most promising tumor treatment method after surgery, radiotherapy, chemotherapy, and targeted therapy. 

Cell therapies represented by CART have shown high response rates in hematological tumors, and tumor vaccines represented by new antigen vaccines have also made positive progress in clinical research. Immune Checkpoint inhibitors represented by PD-1 antibodies have also shown good therapeutic effects in various tumors.

The Emergence of Peptide Vaccines

However, due to the high molecular weight and long half-life of antibody drugs, it is difficult for patients to withdraw drugs in a timely manner once they develop resistance. The molecular weight of peptide drugs is between protein macromolecules and small molecule compounds, and they have a short half-life and high biological safety, making them important candidates for immune checkpoint inhibitors.

In addition, peptides are also the main components that play a role in tumor antigens, and the development of peptide vaccines will also bring hope to cancer patients.

Keywords: tumor, immunotherapy, peptide drugs, peptide vaccines, immune checkpoints

Problems With Peptide Molecules

In recent years, in addition to immune checkpoint inhibitors represented by monoclonal antibodies, peptide drugs have also gradually attracted attention. Traditional peptide drugs composed of L-shaped natural amino acids are prone to enzymatic degradation in the body and difficult to administer orally, which are two major challenges limiting their clinical application.

This article summarizes the research progress and application of peptide drugs in immune checkpoint inhibitors, including single target peptide blockers, bifunctional peptide blockers, self-assembled peptides, and the application of immune checkpoint peptides in tumor diagnosis, providing new ideas for the application of peptide drugs in tumor immunotherapy.

1. Single Target Peptide

High throughput display screening technology plays a very important role in the screening of immune checkpoint blocking peptides. Tao et al. used phage display technology to screen and obtain peptide P-F4 targeting PD-1; Liu et al. used the same method to obtain peptide CLP002 targeting PD-L1.

However, the above peptides are linear peptides composed of L-shaped amino acids, with poor conformational and anti enzymatic stability. In order to synthesize more stable peptides, cyclic peptides are a good choice. The Omizzur Peptide research team used a phage displayed cyclic peptide library to obtain a cyclic peptide blocker C8 targeting PD-1, which can exert good anti-tumor effects in various tumor models. PD-1/PDL1 peptide blockers are expected to provide highly promising candidate drugs for tumor immunotherapy.

2. Bifunctional Peptides

Bispecific antibodies are currently a hot topic in the research and development of antibody drugs, and multiple bispecific antibodies have been approved by the US Food and Drug Administration (FDA) for clinical research. Similar to bispecific antibodies, bifunctional peptides couple peptide molecules targeting two functionally related or complementary targets. The coupled peptides not only retain the functional activity of single target peptides, but also increase their stability and half-life.

Compared with single target peptides, bifunctional peptides can simultaneously function for different signal transduction in organisms, and reasonable design of different target peptides can also achieve a 1+1>2 effect. Compared to bispecific antibodies, the design and synthesis of bifunctional peptides are more convenient.

The Omizzur team recently coupled the smallest active fragment of the PD-1/PD-L1 blocking peptide OPBP-1 with the anti angiogenic peptide DA7R to design a bifunctional blocking peptide.

3. Self-assembled Peptides

Through reasonable design, specific sequence peptides can also self-assemble and construct drug delivery systems. Wang et al. utilized G7 peptide (GNNQQNY) with self-assembly function to target CD3 peptides and integrins α V β The RGD peptide of 3 forms a bifunctional peptide anti CD3-G7-RGD, which targets the CD3 receptor of T cells while utilizing the characteristics of G7 peptide in situ self assembly to form nano oligomers, inducing CD3 receptor oligomerization and activating T cells.

Moreover, the RGD sequence of bifunctional peptides can guide T cells to accurately recognize and kill tumor cells.

4. Nuclide Labeled Peptides

The effectiveness of tumor immunotherapy by blocking immune checkpoints is closely related to the expression of immune checkpoints. Screening patients by detecting the expression level of immune checkpoints can promote precise treatment. Immunohistochemistry is currently the gold standard for detecting the expression of immune checkpoints.

At present, the application of radiolabeled immune checkpoint antibodies or peptides in PET imaging and optical imaging has been extensively preclinical and preliminary clinical studies, demonstrating their potential as dynamic monitoring and prognostic tools for patient stratification, efficacy, and prognosis. Among them, low molecular weight peptides as diagnostic probes have good characteristics such as strong permeability to solid tumors, small adverse reactions, and suitable half-life. Their application in PET imaging has already emerged, and will also provide powerful tools for clinical diagnosis and adjuvant treatment of tumor patients.

FAQs: What are Immune Checkpoint Inhibitors?

Immune checkpoint inhibitors are a new method of immunotherapy, which does not simply refer to improving the body’s immune system, but rather achieves anti-tumor goals by improving the immune microenvironment around tumors, thereby activating the activity of immune cells in the body.

At present, immune checkpoint inhibitors have sparked a wave of treatment in multiple tumors and have made significant clinical progress, including lung cancer, lymphoma, melanoma, colon cancer, and multiple tumor treatments.

Currently, the relatively successful development of immune checkpoint inhibitors is mainly focused on PD-1 monoclonal antibodies and PD-L1 monoclonal antibodies. In addition, there are other new biomarkers for immune checkpoint inhibitors. In research and clinical trials, including TIGIT and LAG-3, they are targeted immune checkpoint inhibitors. Through the treatment of immune checkpoint inhibitors, currently PD-1 antibodies in clinical practice include Paberizumab, Navulizumab, Sinilizumab, Karelizumab, etc; Antibodies to PD-L1 include Duvalizumab and Atilizumab.

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