This approach has received a great deal of attention due to the rapid growth in bioinformatics understanding about peptides. In the past, peptide-based drugs were not widely used due to their limitations such as low selectivity and rapid degradation within biological systems. Recent advances in peptide therapies are exciting and have excellent antitumor effectiveness. There are many new peptide-based anti-tumor therapeutics being developed. This blog will give a brief introduction to anti-tumor drugs based on peptides.
- Immunotherapy against cancer using peptide drugs
Cancer research is dominated by peptide drugs. PD-L1 can be overexpressed by cancer cells. Cancer cells can escape immune response when it binds to PD-1 expressing cells. Immunotherapy may work by blocking the PD-1/PDL1 interaction. D-PPA is a hydrophilic D-type peptide. It can inhibit tumor growth and block the PD-1/PD-L1 interactions in mice bearing CT26. It can also extend their lives.
Macrophages, which are immune cells, play an important role in both acquired immunity and innate immunity. CSF-1R affects the survival and differentiation of macrophages. In a recent study, a peptide called M2pep[Cys-YeqDPwGVKWWY] was modified to improve specificity against M2 TAMs. Experimental results revealed that CSF-1R and M2pep siRNA co-encapsulated M2 TAMs and remodeled them into M1 phenotypes, increasing the anti-tumor immune response.
- Peptide drugs that target Apoptosis
Some peptides can cause cancer cell death. A cancer-fighting peptide called RAV (deoxy bouvardin) can cause mitochondrial apoptosis in cancer cells. Dolastatin10 is another pentapeptide that can cause apoptosis by up-regulating cytochrome C and Bax.
KLA (KLAK KLAK), a proapoptotic peptide, causes programmed cell death by disrupting the mitochondrial membrane. Bioconjugates contain KLA peptides. KLA can bind to the tumor-homing (CRGD GPDC) peptide to increase the permeability of tumor cells and tissue. The potent antitumor effects have been demonstrated in mouse models. These studies may lead to the testing and development of targeted PDCS.
Another example of KLA-based therapy is penetration. It’s a cell-penetrating peptide protein-KLA conjugate. Penetratin and KLA peptides were linked through disulfide bonding to overcome low cellular permeability. The result was high cellular permeability, and even cytotoxicity at low doses. The Penetratin/KLA conjugate has no effect on the normal mitochondria of cells, indicating its potential therapeutic use.
- Peptides for tumor enhancement
In addition, new studies have described new ways to target tumors with peptides. ALOS-4 is a S-S bridged-cyclic (ALOS-4) peptide that targets the integrin AVB3, a protein found in metastatic melanomas. In this study, ALOS-4 was coupled with the topoisomerase I inhibitor Camptothecin. The conjugate demonstrated potent antitumor activity in metastatic human melanoma cells, but was low-toxic to normal tissues. The four-branched branched peptides NT4 were also combined with paclitaxel by a research team. NT4 peptides can bind to tumor membrane glycosaminoglycans sulfate. It becomes more selective against cancer cells when combined with paclitaxel. Its anti-tumor properties are enhanced by this combination.
A second study looked at the tumor-targeting of albumin-binding peptides. In vitro studies showed that bioconjugation of DICLPRWGCLW to a stable complex albumin could be a factor in tumor targeting. The SCC7 model also showed a high level of tumor targeting, as well as a significantly longer half-life. Based on the positive correlation of tumor growth with albumin uptake and a new therapeutic approach to target cancer tissues, it is expected that albumin binding will be used.
- Combination of small cytotoxic drugs and peptide drugs
The development of therapeutic compounds based on peptides is possible by combining cytotoxic drugs with other therapeutic agents.
Many studies have shown that cytotoxic drugs may be bound to peptides with additional functions. Platinum-based cisplatin chemotherapy is a popular cancer treatment. Cisplatin resistant means that cisplatin can be less effective when used long-term. Peptides could be an effective way to combat drug resistance. When cisplatin is combined with peptides, the binding induces a high accumulation of cisplatin in tumors and metastasis-containing organs and significantly reduces the systemic toxicity of cisplatin.
Clinical trials are underway to test peptide-drug combinations for the treatment of cancers that have refractory responses. On February 27, 2021, FDA approved Melflufen for the treatment of multiple myeloma. Melflufen is lipophilic, which makes it easy for cancer cells to ingest. Melflufen molecules can be cleaved using aminopeptidase. This enzyme is found in myeloma cancer cells. It releases toxic chemicals which alkylate tumors and damage DNA. Many forms of peptide conjugates are in active development.
Creative Peptides’ Perspectives
Researchers have begun to understand the limitations of peptide drugs and are now able to draw attention to their powerful anti-tumor effects. Researchers are beginning to recognize the limitations of peptides and can now draw attention to their powerful anti-tumor properties. It is now possible to create therapeutic strategies that combine antitumor drugs and functional peptides. These peptides are expected to have a higher efficiency than antibodies and small molecule drugs.
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