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Neoepitopes or neoantigens are a spectrum of unique mutations presented in a particular patient’s tumor. Neoepitope-based adoptive therapies have the potential of tumor eradication without undue damaging effect on normal tissues. In this context, methods based on the T cell receptor (TCR) engineering or chimeric antigen receptors (CARs) have shown great promise. This review focuses on the TCR-like CARs and TCR-CARs directed against tumor-derived epitopes, with a concerted view on neoepitopes. We also address the current limitations of the field to know how to harness the full benefits of this approach and thereby design a sustained and specific antitumor therapy.

Rheumatoid arthritis (RA) is considered a chronic systemic, multi-factorial, inflammatory, and progressive autoimmune disease affecting many people worldwide. While patients show very individual courses of disease, with RA focusing on the musculoskeletal system, joints are often severely affected, leading to local inflammation, cartilage destruction, and bone erosion. To prevent joint damage and physical disability as one of many symptoms of RA, early diagnosis is critical. Auto-antibodies play a pivotal clinical role in patients with systemic RA. As biomarkers, they could help to make a more efficient diagnosis, prognosis, and treatment decision. Besides auto-antibodies, several other factors are involved in the progression of RA, such as epigenetic alterations, post-translational modifications, glycosylation, autophagy, and T-cells. Understanding the interplay between these factors would contribute to a deeper insight into the causes, mechanisms, progression, and treatment of the disease. In this review, the latest RA research findings are discussed to better understand the pathogenesis, and finally, treatment strategies for RA therapy are presented, including both conventional approaches and new methods that have been developed in recent years or are currently under investigation.

Melanoma is the most aggressive of skin cancer derived from genetic mutations in the melanocytes. Current therapeutic approaches include surgical resection, chemotherapy, photodynamic therapy, immunotherapy, biochemotherapy, and targeted therapy. However, the efficiency of these strategies may be decreased due to the development of diverse resistance mechanisms. Here, it has been proven that therapeutic monoclonal antibodies (mAbs) can improve the efficiency of melanoma therapies and also, cancer vaccines are another approach for the treatment of melanoma that has already improved clinical outcomes in these patients. The use of antibodies and gene vaccines provides a new perspective in melanoma treatment. Since the tumor microenvironment is another important factor for cancer progression and metastasis, in recent times, a mechanism has been identified to provide an opportunity for melanoma cells to communicate with remote cells. This mechanism is involved by a novel molecular structure, named extracellular vesicles (EVs). Depending on the functional status of origin cells, exosomes contain various cargos and different compositions. In this review, we presented recent progress of exosome applications in the treatment of melanoma. Different aspects of exosome therapy and ongoing efforts in this field will be discussed too.

Naringenin is an important phytochemical which belongs to the flavanone group of polyphenols, and is found mainly in citrus fruits like grapefruits and others such as tomatoes and cherries plus medicinal plants derived food. Available evidence demonstrates that naringenin, as herbal medicine, has important pharmacological properties, including anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. Collected data from in vitro and in vivo studies show the inactivation of carcinogens after treatment with pure naringenin, naringenin-loaded nanoparticles, and also naringenin in combination with anti-cancer agents in various malignancies, such as colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancer, bladder neoplasms, gastric cancer, and osteosarcoma. Naringenin inhibits cancer progression through multiple mechanisms, like apoptosis induction, cell cycle arrest, angiogenesis hindrance, and modification of various signaling pathways including Wnt/β-catenin, PI3K/Akt, NF-ĸB, and TGF-β pathways. In this review, we demonstrate that naringenin is a natural product with potential for the treatment of different types of cancer, whether it is used alone, in combination with other agents, or in the form of the naringenin-loaded nanocarrier, after proper technological encapsulation.

Saffron is a spice which is isolated from the dried stigmas of Crocus sativus L. with plentiful of beneficial pharmacological effects including chemopreventive and anticancer properties that are mainly linked to the rich presence of carotenoids in particular crocin, crocetin, picrocrocin and safranal. The mechanism of carotenoids chemopreventive features includes apoptosis, antioxidant activity, improving cell differentiation, modulating carcinogen metabolism, immune modulation, regulating the progression of cell cycle and growth, stimulating the communications of cell-to-cell gap junctions, and inhibiting cell proliferation. Numerous preclinical studies were performed on cancer animal models and cancerous cell lines which confirmed the favorable anticancer properties of saffron on a variety of cancers. Additionally, saffron has been shown to provide protective effects against toxicities associated with several cancer chemotherapeutic agents. Moreover, the key saffron compounds crocin and crocetin can have a synergetic effect when used with other conventional anticancer drugs, thus, improving the efficacy of these drugs in cancer therapy. Furthermore, several studies encapsulated crocin, crocetin, or safranal within nanocarriers to enhance their effectiveness in cancer therapy by overcoming physicochemical limitations. In the present chapter, we aim to give an overview of the mechanism involved in the promising anticancer effects of saffron and its main carotenoids and their applications in preventing and treating several types of cancers.

Neoepitopes or neoantigens are a spectrum of unique mutations presented in a particular patient's tumor. Neoepitope-based adoptive therapies have the potential of tumor eradication without undue damaging effect on normal tissues. In this context, methods based on the T cell receptor (TCR) engineering or chimeric antigen receptors (CARs) have shown great promise. This review focuses on the TCR-like CARs and TCR-CARs directed against tumor-derived epitopes, with a concerted view on neoepitopes. We also address the current limitations of the field to know how to harness the full benefits of this approach and thereby design a sustained and specific antitumor therapy.

Statins are long known class of medicines and the most frequently prescribed drugs in cardiovascular pharmacotherapy, widely ordered not only in patients suffering from dyslipidemia, but also in patients with coronary artery disease, acute coronary syndromes, diabetes mellitus, stroke, hypertension, and chronic kidney disease, with or without coexisting dyslipidemia. However, several clinical trials have shown, that the advantages of statins goes beyond their reduction of the cholesterol level. Some crucial isoprenoid mediators which are highly essential for the activation of different intracellular/signaling proteins, that play important roles in multiple cellular mechanisms, are regulated by statins in addition to the inhibition of cholesterol biosynthesis. Moreover, anti-inflammatory intermediates and cytokines such as c-reactive protein, IL1, IL6, IL8, TNFA are affected downstream targets. Still, these numerous effects of statins such as anti-inflammatory effects, antioxidant effects, anti-proliferative, apoptotic, cell cycle regulatory and immunomodulatory effects, are primarily seen in conjunction with the inhibition of the HMG-CoA reductase. Other direct targets are missing. Beyond the classical application of statins, they were also tested to treat cancer with promising prospects, but still on a level of an adjuvant therapy option. Nevertheless the growing number of cancer studies and the increasing number of molecular players in affected pathways illustrates, that statins might be helpful in cancer therapeutics, despite the major part of the biological reaction network, which is regulated by statins, remains sketchy. It seems, that the statins still have some potential to improve established therapeutic procedures.