Search

Recent advances in immunotherapeutic modalities have profoundly changed the prospect of cancer treatment. These modalities mainly focus on modulating the immune response toward tumor cells by using monoclonal antibodies, cancer vaccines, adoptive cell transfer or combination of these methods. In the last few years, Iranian scientists have conducted several projects in these arenas. Here, we provide an overview of these studies and analyze the quality and trend of publications in each sub-specialty of the field. In addition, the contribution of different universities and scientific institutes is assessed. This study may benefit scientific community and policymakers to plan future cancer immunotherapies in Iran and other countries., (Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

CAR-T cell therapy has shown remarkable promise in treating B-cell malignancies, which has sparked optimism about its potential to treat other types of cancer as well. Nevertheless, the Expectations of CAR-T cell therapy in solid tumors and non-B cell hematologic malignancies have not been met. Furthermore, safety concerns regarding the use of viral vectors and the current personalized production process are other bottlenecks that limit its widespread use. In recent years the use of gene editing technology in CAR-T cell therapy has opened a new way to unleash the latent potentials of CAR-T cell therapy and lessen its associated challenges. Moreover, gene editing tools have paved the way to manufacturing CAR-T cells in a fully non-viral approach as well as providing a universal, off-the-shelf product. Despite all the advantages of gene editing strategies, the off-target activity of classical gene editing tools (ZFNs, TALENs, and CRISPR/Cas9) remains a major concern. Accordingly, several efforts have been made in recent years to reduce their off-target activity and genotoxicity, leading to the introduction of advanced gene editing tools with an improved safety profile. In this review, we begin by examining advanced gene editing tools, providing an overview of how these technologies are currently being applied in clinical trials of CAR-T cell therapies. Following this, we explore various gene editing strategies aimed at enhancing the safety and efficacy of CAR-T cell therapy. [ABSTRACT FROM AUTHOR]

Currently, adoptive immunotherapy is considered as one of the leading treatments in cancer. Successful adoptive immunotherapy depends on producing large numbers of desired T cells ex vivo for infusion. This requires an effective protocol for maximum functional T‐cell expansion while keeping the time and costs to a minimum. Current T‐cell expansion protocols are diverse in their methodology, and a universal protocol of expansion is wanting. Also, new findings regarding T‐cell biology, signaling, and activation have reshaped the strategies of T‐cell propagation over the years, introducing new ways to expand T cells. Here, we reviewed different conditions for blood‐derived polyclonal T‐cell expansion so as to elucidate the influential factors of T‐cell expansion and their efficacy. [ABSTRACT FROM AUTHOR]

Background: Xenogeneic graft-versus-host disease (xGvHD) is an inevitable confounder of preclinical evaluation of adoptive immunotherapies on tumor-bearing immunodeficient mouse models. This study was designed to appraise the clinical and histopathological effects caused by xGvHD in severely immunodeficient mice considering the T cell dosage. Methods: Fifty NOG mice underwent intraperitoneal injection of three different doses of human-derived total T cells, a high dose of CD8+T cells, or vehicle (as control). Clinical and histopathological status of the study subjects were evaluated and compared according to scoring systems. Results: In mice receiving higher doses of total T cells, the clinical severity of xGvHD was greater. However, recipients of CD8+T cells developed none to mild xGvHD manifestations. Higher doses of T cells were associated with poorer outcomes including premature death and more severe histopathologic damages. Greater CD3+T cell tissue engraftment (immunohistochemical CD3 positivity) was associated with more severe xGvHD-induced histopathological damages. Clinical xGvHD scores were significantly correlated with histopathological xGvHD scores in total and in each tissue. Mice with severe cutaneous symptoms had higher scores of xGvHD-induced histopathologic changes in the skin. Lethargy was associated with higher histopathological scores in the lungs, liver and spleen. Conclusion: In preclinical evaluations, lower doses of T cell-based therapies are associated with milder xGvHD. Development of xGvHD may be averted by the use of CD4+T cell-depleted grafts. Histopathological and clinical scoring systems for evaluating xGvHD are significantly correlated. The lungs and liver are reliable organs for histopathological assessment and scoring of xGvHD. [ABSTRACT FROM AUTHOR]

Adoptive cell therapy (ACT) using tumor antigen-independent killer cells has been widely used in clinical trials of cancer treatment. Circumventing the need for identification of a particular tumor-associated antigen on tumor cells, the approach has opened possibilities for the extension of ACT immunotherapy to patients with a wide variety of cancer types. Namely, Natural Killer (NK), Lymphokine-activated Killer (LAK) cells and Cytokine-induced killer (CIK) cells are the most commonly used cell types in antigen-independent adoptive immunotherapy of cancer. They all originate from peripheral blood mononuclear cells and share several common features in their killing mechanisms. However, despite broad application in clinical settings, the boundaries between these cell types are not very clearly defined. The current study aims to review different aspects of these cell populations in terms of phenotypical characteristic and preparation media, to clarify how the boundaries are set. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cell therapy is anticipated to be increasingly implemented in the context of cancer treatment after two current FDA approval of anti-CD19 CAR-T cells (Kymriah™ & Yescarta™). The success of CD19 is mainly attributable to the proper selection of the antigen, CD19, as the target of the disease, highlighting the importance of target selection for other CAR therapies. Therefore, here we performed a global analysis of targets that are the prime focus for various CAR T cell therapies in human clinical trials. [ABSTRACT FROM AUTHOR]