Constitutionist and nationalist intellectuals were the first group that discussed modernism in literature theoretically, emphasizing the necessity of literary modernism, based on their political and social ideas. The movement of literary modernism came to develop and two movments of literary medernim, the conservatist and radical movements, appeared. Taqi Rafàt was one of the prominent writers and poets in the radical movement. This research studies components of modernism in Rafàt’s poetry from three points of view: the style of expression, identity of the sender and the receiver and their relation, and the subject, and attempts to answer the questions that what aspects of modernism are in Rafàt’s poetry and what relationship is between modernist instances in his poetry and his contemporary modernist social and political movements. Study of his poetry shows that there are prominent aspects of modernism in his poetry from the three points of view and so modernism could be known as the centre component in it. These modern aspects have a dialectical relationship with social and political modernism, of wich the Iranian nationalism movement and the Constitutionism movement were supporters.

Redirected chimeric antigen receptor (CAR) T-cells can recognize and eradicate cancer cells in a major histocompatibility complex independent manner. Genetic engineering of T cells through CAR expression has yielded great results in the treatment of hematological malignancies compared with solid tumors. There has been a constant effort to enhance the effectiveness of these living drugs, due to their limited success in targeting solid tumors. Poor T cell trafficking, tumor-specific antigen selection, and the immunosuppressive tumor microenvironment are considered as the main barriers in targeting solid tumors by CAR T-cells. Here, we reviewed the current state of CAR T-cell therapy in breast cancer, as the second cancer-related death in women worldwide, as well as some strategies adopted to keep the main limitations of CAR T-cells under control. Also, we summarized various approaches that have been developed to enhance the therapeutic outcomes of this treatment in solid tumors targeting.

According to the growing developments and improvements of cancer immunotherapies, nowadays, special attention has been paid to the immunotherapies of various types of cancers. Chimeric antigen receptor (CAR) T-cell therapy is one of the T-cell therapies that affects tumor cells, not the normal cells. Research conducted over the past decades suggests that CAR T-cell based therapies has revolutionized cancer therapies, and has provided precious achievements in the treatment of hematologic malignancies such as leukemia and lymphoma, and solid tumors including neuroblastoma and glioblastoma. In this review article, structure, function of CAR T- cells, along with some of the antigens that are expressed on the surface of the tumor cells and the CAR T-cells targeting them are presented. Subsequently, several examples of successful therapies with the help of this technology are presented and finally, the safety of these therapies and the challenges and future perspectives are discussed.

We report a case of a 76-year-old male with a history of relapsed and refractory diffuse large B-cell lymphoma (DLBCL).Our patient was initially treated with front line chemotherapy along with central nervous system (CNS) prophylaxis with complete response. He subsequently relapsed, was sensitive to second-line chemotherapy, and underwent autologous stem cell transplantation achieving a complete remission. Only a few months after transplant, the patient suffered his second relapse and was deemed a candidate for Chimeric Antigen Receptor T-Cell Therapy (CAR-T). Given his aggressive disease, combined with the time needed to generate CAR-T cells, a multidisciplinary team recommended to treat our patient with liposomal vincristine in combination with rituximab as a bridge therapy. Durable responses have been seen using liposomal vincristine based on results from a recent phase II trial in heavily pretreated patients with DLBCL1. This therapy was effective in stabilizing and reducing active disease in our patient. This case looks to illustrate the use of liposomal vincristine in combination with immunotherapy in a novel setting bridging highly selected patients with active and refractory lymphoma prior to CAR-T. Moreover, we expanded an additional therapeutic point, highlighting the importance of optimal disease control prior to CAR-T cell harvesting, as recent literature has shown that residual malignant cells in the pheresis product may be inadvertently be transfected with the CAR gene, resulting in resistance and further relapse2.

Dear editor Acute lymphoblastic leukaemia (ALL) is a prevalent and highly progressive cancer in children and adolescents, associated with an excessive production of immature lymphocytes in the bone marrow, which leads to a negative effect on the production of other blood components such as red blood cells, platelets and other white blood cells (1-3). The survival rate of this cancer was only 10% in children in the 1960s, but this had reached 90% by 2015, although still remains at 80-90% in the very young (2, 4-6). Chemotherapy is the primary treatment for ALL along with auxiliary therapies to help with its severe side effects, but hematopoietic stem cell transplantation and immunotherapy are two emerging and promising approaches in the treatment of this cancer (6-9). Immunotherapy for pediatric ALL consists of using genetically modified T cells, called chimeric antigen receptor (CAR) T-cells, which are autologous or allogeneic immune T cells that have been produced to better identify and eliminate more specific cancer cells via the targeting of one or several proteins related to cancer, notably CD19 and CD22 or both (figure 1) (6, 10). According to data presented by clinicaltrials.gov, twelve clinical studies have performed on pediatric leukaemia, especially ALL, using CAR T-cell on approximately 394 patients until 2018. However, all of these clinical trials are in the early stages (Phase I or Phase I/II) (6). Considering to data obtained from clinicaltrials.gov, ten out of twelve studies were used of CD19-targeted CAR T cells while CD22-targeted CAR T cells involved in four studies (6). Furthermore, in a Phase I clinical trial study, it was demonstrated that Bicistronic Chimeric Antigen Receptor (CAR) T-Cell Therapy which called to AUTO3, could promising as a better solve for Therapy in paediatric patients with refractory or relapse (R/R) B cell ALL, due to targeting of CD19 and CD22 at the same time (11). Similarly, a Phase I clinical trial study indicated efficiency and safety of bispecific CAR T-cell which simultaneous targeting of CD19 and CD22 in pediatric patients with ALL (12). This data along to others previously reported studies demonstrated potential capacity of CAR T-cell in leukaemia, especially ALL (6, 13, 14). In addition, tisagenlecleucel (Kymriah™), an autologous CD19-targeted CAR T cell, recently introduced as a Food and Drug Administration (FDA) and European :::::union::::: (EU) approved cell-based therapy product for use in paediatric patients with refractory or relapse (R/R) B cell precursor ALL (15-19). According to obtained results, 83% patients have demonstrated a partial or complete response to treatment using single injection of tisagenlecleucel in short period (20). Besides the high response rate to treatment, the length of time after primary treatment without certain complications or events in pediatric patients with ALL, and theirs overall survival, was higher for tisagenlecleucel-based treatment than other cancer treatment approaches (21). However, the long-term efficiency and safety of this approach, is still unclear and remains as a challenge (20). In addition, cytokine release syndrome, neurological toxicity and other toxicities are so far recognized as the most commonly known complications of this method (22). Furthermore, cardiovascular and neurodegenerative disorders can be attributed to the toxic effects of CAR T-cells on patients (23). As a result, this modern treatment should be employed along with specialized medical care by a medical group with different expertise and all the required facilities to certify optimal patient consequences (23). additionally, the cost of this treatment is very high for patients, approximately 282,000 euro per patient (24). Altogether, CAR T-cells by identifying and killing the cancer cell could help in treatment of ALL patient’s and reverse the processes of disease, which makes it as a great and new approach in cancer therapy (6). Results of clinical studies have demonstrated its potential, suggesting that CAR T-cells could be indeed used as an innovative and successful treatment for childhood ALL, where chemotherapy has failed.

Today, treatment with CAR-T cells is accepted as an effective treatment for blood malignancies. CAR-T cells are autologous T cells that are engineered by gene transfer techniques to express a chimeric antigen receptor (CAR). Despite the promising results and the approval of six CAR-T cell products; these products have not yet been approved for solid tumors. In addition, the high cost of treatment with CAR-T cells has limited patients' access to these life-saving drugs. Therefore, key considerations in the design and development of CAR-T cells should be defined and methods of reducing the cost of this treatment method should be investigated.

This study was performed based on an accurate bibliography through research databases such as PubMed, Scopus, Web of Science, and Google Scholar search engine, as well as the websites of pharmaceutical companies.

CAR synthetic receptors contain an antigen-recognizing extracellular region that connects to the space-forming, transmembrane and intracellular messenger regions. Each part of the CAR structure affects some functions of CAR, including target recognition, activation and cell lysis. So far, five generations of CAR-T cells have been developed to improve the messaging capacity of these cells. In addition, gene transfer systems such as electroporation, transposon and genome editing systems have been introduced as an alternative to viral vectors to produce safe and affordable CAR-T cells. Also, the development of ready-to-use products, product production in places far from the place of consumption, new pricing platforms and methods, and health insurance system initiatives have been suggested as ways to reduce prices.

In this article, an overview of how to develop CAR-T cells, important factors in the design of chimeric receptors, different methods of gene transfer and solutions to reduce the cost of this treatment were discussed. By using these strategies, the potential of CAR-T cells in cancer immunotherapy can be fully utilized.

The most often diagnosed and fatal malignancy in women is breast cancer. The International Agency for Research on Cancer (IARC) estimates that there are 2.26 million new cases of cancer in 2020.  Adoptive cell therapy using T cells with chimeric antigen receptor shows potential for the treatment of solid tumors, such as breast cancer.  In this work the effectiveness of CAR-T cells against monolayer and three-dimensional bioprinted tumor-like structures made of modified MCF-7 breast cancer cells was assessed. The cytokine profile of supernatants after co-cultivation of MCF-7 tumor cell models with CAR-T cells was also measured to reveal the inflammatory background associated with this interaction.

 Lymphoma, the most predominant neoplastic disorder, is divided into Hodgkin and Non-Hodgkin Lymphoma classifications. Immunotherapeutic modalities have emerged as essential methodologies in combating lymphoid malignancies. Chimeric Antigen Receptor (CAR) T cells exhibit promising responses in chemotherapy-resistant B-cell non-Hodgkin lymphoma cases.

 This comprehensive review delineates the advancement of CAR-T cell therapy as an immunotherapeutic instrument, the selection of lymphoma antigens for CAR-T cell targeting, and the conceptualization, synthesis, and deployment of CAR-T cells. Furthermore, it encompasses the advantages and disadvantages of CAR-T cell therapy and the prospective horizons of CAR-T cells from a computational research perspective. In order to improve the design and functionality of artificial CARs, there is a need for TCR recognition investigation, followed by the implementation of a quality surveillance methodology.

 Various lymphoma antigens are amenable to CAR-T cell targeting, such as CD19, CD20, CD22, CD30, the kappa light chain, and ROR1. A notable merit of CAR-T cell therapy is the augmentation of the immune system’s capacity to generate tumoricidal activity in patients exhibiting chemotherapy-resistant lymphoma. Nevertheless, it also introduces manufacturing impediments that are laborious, technologically demanding, and financially burdensome. Physical, physicochemical, and physiological limitations further exacerbate the challenge of treating solid neoplasms with CAR-T cells.

 While the efficacy and safety of CAR-T cell immunotherapy remain subjects of fervent investigation, the promise of this cutting-edge technology offers valuable insights for the future evolution of lymphoma treatment management approaches. Moreover, CAR-T cell therapies potentially benefit patients, motivating regulatory bodies to foster international collaboration.

Immunotherapy with genetically engineered T-cells that express the chimeric antigen receptor (CAR) has raised hopes for the treatment of pediatric malignancies. Although CAR T-cell development is on a fast-moving pace and evolution, the context of exploring novel targetable antigens has been neglected. In this review study, we analyze the prominent hematologic antigens targeted by engineered T-cells in both preclinical and clinical aspects. Furthermore, we discuss the outcomes of CAR-based therapy in hematologic cancers from different viewpoints of treatment and provide some critical features for additional considerations.  Almost certainly, most of the engineered T-cells redirected against hematologic disorders aim at conventional target antigens rather than targeting an ideal target antigen that is exclusively expressed on cancerous cells and restricted to normal tissues. CAR-based clinical trials in hematologic cancers have often dealt with CD19, followed by BCMA, CD22, and CD20 antigens. Besides, most of the scFvs used in the CAR structure are derived from murine antibodies, which may raise the concern about immunogenicity by reducing the persistence of modified T-cells. Nevertheless, short- and long-term life-threatening toxicities and the development of escape mechanisms that result in resistance and antigen loss are not thoroughly understood yet. The ultimate goal of using modified CAR T-cells is to make them effective and curative. Therefore, a better understanding of all the features pertaining to target antigens is imperative. Also, the methods to identify candidate target antigens and manage the associated obstacles of CAR T-cells should be evaluated and prioritized.

Despite the success of CAR-T cells in the treatment of hematologic malignancies, the use of allogeneic sources of T lymphocytes to produce these cells is associated with risk of GvHD. Cytokine induced killer (CIK) cells are a population with a lower risk of GvHD. Therefore, CAR-CIK cells can be evaluated as a potential alternative for CAR-T cells.

In this experimental study, after isolation and culture of mononuclear cells isolated from the peripheral blood of two healthy donors, T and CIK cells are transduced with CD19 gene containing lentiviral vector. On the 16th day of culture, to compare the cytotoxicity of CAR-T and CAR-CIK cells, these cells were co-cultured with CD19+ K562 target cells, and the death rate among the target cells was measured using a lactate dehydrogenase release assay kit. Student T-test, Anova and post-hoc Tukey were used for statistical analysis using Graph Pad prism software 8. A p-value less than 0.05 was considered statistically significant.

In both CAR-CIK and CAR-T cell, CAR receptor caused a significant increase in cytotoxicity. So that no significant difference was observed between the cytotoxicity of CAR-T cells (67.8% ± 1.7) and CAR-CIK (65.1% ± 1.8).

Conclusions :

CAR-CIK cells show a suitable in vitro cytotoxicity, so they can be considered as a potential alternative for CAR-T cells. However, more preclinical and clinical studies are needed to compare other effective dimensions in the function of these two cell types.