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Peptide Vaccines in Cancers
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Öznur Özge Özcan, Rümeysa Rabia Kocatürk, Fadime Canbolat
PLGA is also FDA approved for humans, biocompatible, and polymeric NPs. Highly stable in PLGA saline buffer, it is very suitable for skin and intramuscular injections in cancer peptide vaccine applications (Kim, Griffith, and Panyam 2019). Transition-like receptor (TLR) 7/8 agonists are among the important adjuvant groups in cancer vaccines to demonstrate strong T cell responses by promoting DC uptake and are also a citcon enhancer in cellular immune response. Although TLR7 agonists were successful in in vitro cancer vaccination studies, they resulted in their accumulation at the injection site in preclinical and clinical studies. As a solution, although it is thought that by applying subcutaneous and intramuscular applications, TLR7 and TLR8 agonists will be provided with advantage in terms of transmission to DCs that can produce the desired immune response. It has been used with PLGA polymeric NPs that can overcome these problems such as enhancing the DC uptake and lymphatic drainage; PLGA NPs overcome these problems by providing high clearance protection for adjuvant formulations (Silva et al. 2013). Since peptides identified by cancer type and biology are not sufficient to increase T cell stimulation, an immunostimulant is also needed to increase the immunogenicity of the vaccine. For this reason, to increase the immunogenicity of peptide vaccines in cancer, IL-12, granulocyte-macrophage colony stimulating factor (GM-CSF), and TLRs agonists have been actively studied as vaccine adjuvants so far (Lehner et al. 2007; Simons and Sacks 2006; Napolitani et al. 2005).
The Molecular Basis of Bladder Cancer and Prospects for Gene Therapy Using Hammerhead Ribozymes
Published in Eric Wickstrom, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Eric J. Small, Mohammed Kashani-Sabet, David Y. Bouffard, Kevin J. Scanlon
For patients with superficial bladder cancer, intravesical therapy, in which chemotherapeutic or biological agents are instilled into the bladder, is used as an adjunct to TURBT, in order to treat and to prevent recurrences of superficial bladder cancer. The intravesical agent most commonly used in the United States is Bacillus Calmette-Guérin (BCG), which is believed to act as a nonspecific immunostimulant. BCG clearly reduces superficial bladder cancer recurrence. Its effect on tumor progression and survival is less clear. BCG therapy is usually well-tolerated, but can be associated with a number of toxicities, including significant cystitis, hematuria, fever, and BCG sepsis. Patients who fail BCG therapy, either because of continued tumor recurrence or because of toxicity, are often treated with intravesical chemotherapy, such as thiotepa, mitomycin C, doxorubicin, or other intravesical biologic agents such as interferon α Witjes et al., 1996). More recently, an orally administered immunostimulant, bropirimine has become more popular. Nonetheless, despite these maneuvers, many patients continue to go on to muscle invasive disease, necessitating cystectomy.
Recent Insights on the Role of Natural Medicines in Immunostimulation
Published in Dilip Ghosh, Pulok K. Mukherjee, Natural Medicines, 2019
Isabella Muscari, Sabrina Adorisio, Trinh Thi Thuy, Tran Van Sung, Domenico V. Delfino
Resveratrol. This compound is present in foods such as grapevine and red wine. Resveratrol increases the CD4+/CD8+ T-cell ratio (Pozzesi et al. 2007) and enhances T cell proliferation. In addition, this immunostimulant improves the B-cell-mediated immune response and increases the level of serum antibodies. Moreover, resveratrol exhibits a strong stimulatory effect on NK cells and suppresses the release of IL-6, IL-10 and IL-1ra in human PBMCs that were reported to possess tumour promoter activity. Resveratrol shows an inhibitory effect on the expansion and proliferation of Treg suppressor immune cells in the spleen of tumour-bearing mice (Mohamed et al. 2017).
Carbohydrate-containing nanoparticles as vaccine adjuvants
Published in Expert Review of Vaccines, 2021
Xinyuan Zhang, Zhigang Zhang, Ningshao Xia, Qinjian Zhao
One of the most common carbohydrates, sucrose, is used as an immunostimulant in vaccines [35]. Evaluation of immunogenicity of a sucrose-containing nanoparticulate adjuvant was conducted [98,99]. Wang and coworkers synthesized sucrose-containing NPs by taking silica as template [99]. The prepared NPs are uniform and spherical with diameter of 470 nm, which have large mesopores and macropores. Following oral administration of formulations of bovine serum albumin (BSA), significantly higher level of IgA titers was induced by sucrose-containing NPs as compared to Freund’s adjuvant. Besides, high level of IgG2a antibodies was elicited (almost equal to IgG1 titers). These results indicated that these sucrose-containing NPs could induce both mucosal and systematic immune response, which is balanced in Th1 and Th2 [99].
Polymeric nanostructure vaccines: applications and challenges
Published in Expert Opinion on Drug Delivery, 2020
Rosana Simón-Vázquez, Mercedes Peleteiro, África González-Fernández
Collagen is another endogenous protein, highly abundant in the extracellular matrix, that can be used as Ag or immunotherapeutic carrier [71,72]. This protein has associated immunostimulant properties. For instance, collagen I induces the release of chemokine (C-X-C motif) ligand (CXCL)−1 and CXCL−2 in DCs, which have neutrophil chemoattractant activity, and the regeneration of damaged cell membranes, among other functions [72]. Gelatin can be obtained from denaturation and partial acid or alkaline hydrolysis, thermal, or enzymatic degradation of collagen proteins [73]. It has been used also for vaccine development, mainly forming NPs to encapsulate the Ag [73]. Gelatin NPs can be internalized by DCs and other APCs and induce the release of IL-2 and IFN-γ [74,75]. Degradation of the NP by lysosomal collagenase releases the Ag intracellularly and allows Ag processing and presentation by APCs [75].
A historical turning point for the treatment of advanced renal cell carcinoma: inhibition of immune checkpoint
Published in Current Medical Research and Opinion, 2020
Mutlu Hizal, Mehmet A. N. Sendur, Burak Bilgin, Muhammed Bulent Akinci, Didem Sener Dede, Bulent Yalcin
In the twentieth century, many immunomodulatory, immunostimulant agents, and vaccinations were tried in the treatment of different cancer types. However, even the efficacy of the clinically most useful substance IFN in the treatment era of most immunogenic tumors, RCC and melanoma, was highly suspicious16. Thanks to advances in molecular biology, immunology, and genetics, at the turn of the century, Honjo described PD-1 (programmed death-1) in programmed cell death in 1992, and Allison reported antitumor immunity with CTLA-4 blockade in 199617,18. For their discoveries, Honjo and Allison were awarded Nobel prizes later in 2018. During this time, physicians and scientists witnessed astonishing results in almost all types of cancer, especially in tumors with which they had least hope in terms of treatment.