Peptide-based strategies have received an enormous amount of attention because of their specificity and applicability. Their specificity and tumor-targeting ability are applied to diagnosis and treatment for cancer patients. In this review, we will summarize recent advancements and future perspectives on peptide-based strategies for cancer treatment. The literature search was conducted to identify relevant articles for peptide-based strategies for cancer treatment. It was performed using PubMed for articles in English until June 2023. Information on clinical trials was also obtained from ClinicalTrial.gov. Given that peptide-based strategies have several advantages such as targeted delivery to the diseased area, personalized designs, relatively small sizes, and simple production process, bioactive peptides having anti-cancer activities (anti-cancer peptides or ACPs) have been tested in pre-clinical settings and clinical trials. The capability of peptides for tumor targeting is essentially useful for peptide–drug conjugates (PDCs), diagnosis, and image-guided surgery. Immunomodulation with peptide vaccines has been extensively tested in clinical trials. Despite such advantages, FDA-approved peptide agents for solid cancer are still limited. This review will provide a detailed overview of current approaches, design strategies, routes of administration, and new technological advancements. We will highlight the success and limitations of peptide-based therapies for cancer treatment.

Cell-penetrating peptides (CPPs) are short peptides with the ability to translocate through the cell membrane to facilitate their cellular uptake. CPPs can be used as drug-delivery systems for molecules that are difficult to uptake. Ocular drug delivery is challenging due to the structural and physiological complexity of the eye. CPPs may be tailored to overcome this challenge, facilitating cellular uptake and delivery to the targeted area. Retinal diseases occur at the posterior pole of the eye; thus, intravitreal injections are needed to deliver drugs at an effective concentration in situ. However, frequent injections have risks of causing vision-threatening complications. Recent investigations have focused on developing long-acting drugs and drug delivery systems to reduce the frequency of injections. In fact, conjugation with CPP could deliver FDA-approved drugs to the back of the eye, as seen by topical application in animal models. This review summarizes recent advances in CPPs, protein/peptide-based drugs for eye diseases, and the use of CPPs for drug delivery based on systematic searches in PubMed and clinical trials. We highlight targeted therapies and explore the potential of CPPs and peptide-based drugs for eye diseases.

Despite therapeutic advancements, metastatic triple-negative breast cancer (TNBC) remains mostly incurable and is a frequent cause of cancer-related deaths. We tested the hypothesis that inhibiting suppressive signals sustained by transforming growth factor (TGF)-β and concurrently stimulating recruitment of inflammatory cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) by oncolytic viruses would result in improved anti-tumor responses. Thus, we developed a new oncolytic adenovirus rAd.sT.GM (AMUN-003) that expresses both sTGFβRIIFc (a TGF-β decoy), and GM-CSF and tested it in a mouse TNBC (4T1) subcutaneous model. rAd.sT.GM was safe to use and more effective in controlling tumor progression and lung metastasis following intratumoral injections when compared with control adenoviruses without modifications. In the same model, combinations of immune checkpoint inhibitor (ICI) therapy with rAd.sT.GM resulted in better inhibition of tumor growth and metastasis. Furthermore, we examined key immune response and prognosis biomarkers in sera, lungs, spleens, and tumors to evaluate the treatment efficacy. We found several key anti-tumor Th1 cytokines such as interleukin (IL)-2, IL-4, and interferon-γ, were stimulated by the combination therapy either systemically or in tumors or both, as well as anti-tumor biomarkers such as Granzyme B and perforin. These results support advancement to clinical testing with the combination therapy of rAd.sT.GM and ICIs for TNBC patients.