The successful outcomes of chimeric antigen receptor (CAR) T-cell therapy in treating hematologic cancers have increased the previously unprecedented excitement to use this innovative approach in treating various forms of human cancers. Although researchers have put a lot of work into maximizing the effectiveness of these cells in the context of solid tumors, few studies have discussed challenges and potential strategies to overcome them. Restricted trafficking and infiltration into the tumor site, hypoxic and immunosuppressive tumor microenvironment (TME), antigen escape and heterogeneity, CAR T-cell exhaustion, and severe life-threatening toxicities are a few of the major obstacles facing CAR T-cells. CAR designs will need to go beyond the traditional architectures in order to get over these limitations and broaden their applicability to a larger range of malignancies. To enhance the safety, effectiveness, and applicability of this treatment modality, researchers are addressing the present challenges with a wide variety of engineering strategies as well as integrating several therapeutic tactics. In this study, we reviewed the antigens that CAR T-cells have been clinically trained to recognize, as well as counterstrategies to overcome the limitations of CAR T-cell therapy, such as recent advances in CAR T-cell engineering and the use of several therapies in combination to optimize their clinical efficacy in solid tumors.
29 September 2016 in Journal of Biomedical Science
Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mammalian body during a long-standing evolutionary period. The birth of phage display technology has been a turning point in the development of phage-based vaccines. Phage display vaccines are made by expressing multiple copies of an antigen on the surface of immunogenic phage particles, thereby eliciting a powerful and effective immune response. Also, the ability to produce combinatorial peptide libraries with a highly diverse pool of randomized ligands has transformed phage display into a straightforward, versatile and high throughput screening methodology for the identification of potential vaccine candidates against different diseases in particular microbial infections. These libraries can be conveniently screened through an affinity selection-based strategy called biopanning against a wide variety of targets for the selection of mimotopes with high antigenicity and immunogenicity. Also, they can be panned against the antiserum of convalescent individuals to recognize novel peptidomimetics of pathogen-related epitopes. Phage display has represented enormous promise for finding new strategies of vaccine discovery and production and current breakthroughs promise a brilliant future for the development of different phage-based vaccine platforms.
Invasive candidiasis (IC) can affect individuals with various underlying diseases hospitalized in different parts of hospitals. In recent decades, IC has caused 27-55% mortality in general population. Although Candida albicans (C. albicans) is still the most common cause of IC, non-albicans infections such as C. krusei, C. glabrata, C. lusitaniae, C. tropicalis, and C. parapsilosis have been increased in recent years. Treatment of invasive fungal infections is challenging as the number of existing antifungals is limited and more problems include: toxicity, drug interactions, and drug resistance. These problems provide a clear rationale for the development of new immunotherapies to increase outcomes in patients with invasive fungal infections. Thus, the purpose of this paper is to complete review of the current and modern antifungal drugs in IC therapy and focus on the role of immunotherapy in preventing and controlling the disease. Therefore, we review the features of current research efforts directed towards devising safe and effective immunotherapeutic options for fungal infections, including work on antifungal vaccines, engineered T-cells, cytokines, monoclonal antibodies, and other agents.
Food is the essential need of human life and has nutrients that support growth and health. Gastrointestinal tract microbiota involves valuable microorganisms that develop therapeutic effects and are characterized as probiotics. The investigations on appropriate probiotic strains have led to the characterization of specific metabolic byproducts of probiotics named postbiotics. The probiotics must maintain their survival against inappropriate lethal conditions of the processing, storage, distribution, preparation, and digestion system so that they can exhibit their most health effects. Conversely, probiotic metabolites (postbiotics) have successfully overcome these unfavorable conditions and may be an appropriate alternative to probiotics. Due to their specific chemical structure, safe profile, long shelf-life, and the fact that they contain various signaling molecules, postbiotics may have anti-inflammatory, immunomodulatory, antihypertensive properties, inhibiting abnormal cell proliferation and antioxidative activities. Consequently, present scientific literature approves that postbiotics can mimic the fundamental and clinical role of probiotics, and due to their unique characteristics, they can be applied in an oral delivery system (pharmaceutical/functional foods), as a preharvest food safety hurdle, to promote the shelf-life of food products and develop novel functional foods or/and for developing health benefits, and therapeutic aims. This review addresses the latest postbiotic applications with regard to pharmaceutical formulations and commercial food-based products. Potential postbiotic applications in the promotion of host health status, prevention of disease, and complementary treatment are also reviewed.