جستجوی مقالات مرتبط با کلیدواژه « ایمونوتراپی » در نشریات گروه « پزشکی »

Cancer is still a major and leading health problem worldwide. Lack of early detection, chemoresistance and cancer recurrence mean that extensive research and development is needed in this area.

This review study was conducted based on the Prism protocol and searching in international databases (PubMed, Google Scholar, Science). According to the desired strategy, all articles published in English until September 2022 were evaluated using the keywords "microenvironment", "cancer" and "cathepsin D" and the combination of these search words and selected articles with the PRISMA checklist.

The complexity of the tumor microenvironment in the biological environment creates greater challenges for safe, selective and targeted treatments. Existing strategies such as chemotherapy, radiotherapy and anti-angiogenic treatments improve the survival of patients without disease progression and moderately, however, they are all associated with side effects. Therefore, targeting potential candidates in the microenvironment, such as extracellular cathepsin D (CathD), which plays an important role in the development of breast and ovarian cancer, can be a breakthrough in cancer treatment, especially with the use of new therapeutic methods such as immunotherapy and nanotechnology-based therapy.

Finally, in this review study on CathD, the general conclusion was that this compound can be carefully investigated by researchers as a pro-cancer agent and specifically as a pro-angiogenic agent that functions functionally in the tumor microenvironment. take Therefore, possible ways to target this protein as a new therapeutic target compound are discussed and reviewed in research works based on laboratory and clinical processes

Candida albicans is the most common cause of invasive candidiasis, but in recent years the incidence of infections caused by other species such as Candida Kruzei, Candida glabrata, Candida tropicalis, Candida parapsilosis and Candida lusitania has increased. In the last decade, the treatment methods for invasive candidiasis have changed completely, and a successful treatment depends on the timely start of treatment, the selection of an effective drug, and the lack of resistance of the fungus to that particular drug. On the other hand, the widespread use of immunosuppressive drugs as well as organ transplants has all caused widespread problems in the treatment of invasive candidiasis. Together, these observations highlight a rationale for the immediate development of new immunotherapy methods to enhance antifungal therapy in immunocompromised hosts. The past decade has seen great advances in our understanding of fungal immunobiology, leading to a number of new molecular and cellular immunotherapy methods for invasive fungal infections. Therefore, the aim of this study was to review the common and new antifungal drugs in the treatment of invasive candidiasis and to discuss the role of immunotherapy in better prevention and control of the disease.

In recent years, immunotherapy using chimeric antigen receptor T cells (CAR T cells) has been considered as a novel and promising treatment for some diseases, especially cancer. The CAR T cell production is a multi-step, complex, time-consuming, and costly process. One of the most important steps in production of CAR T cells is expansion of these cells at appropriate numbers for injection. Therefore, the aim of this study was to investigate the methods of expansion for human CAR T cells in ex vivo.

In this study, specifically engineered CAR T cells against the MUC1 tumor antigen were prepared. The cells were then treated with rIL-2, anti-CD3/C28 Dynadeads, and allogeneic PBMC (Rapid expansion protocol (REP)) for 14 days.

The results showed that using anti-CD3/CD28 antibodies in effective ratios; 1: 1 and 1: 3 (bead: cell) along with (IU100) rIL-2 resulted in a 27.5-fold increase in the number of cells. However, the use of rIL-2 alone or allogeneic PBMC eventually resulted in 4.5-fold increase and 9-fold increase, respectively.

Anti-CD3/CD28 in combination with rIL-2 can provide all three signals required for T cell activation and proliferation which can be a suitable alternative to costly and expensive cell proliferation techniques for animal or human CAR T cell studies.

Introduction Mesenchymal stem cells (MSCs) are present in most tissues of the body. These cells are involved in various biological processes, such as maintaining tissue homeostasis and wound healing. Recent studies have shown that tumor associated MSCs (TA-MSCs) are also present in tumor microenvironment (TME) of most solid tumors. MSCs have a strong tendency to migration toward tumor tissues. Once entering are TME, MSCs educated by tumor cells and other factors in the TME and become TA-MSCs. Study of the relationship between MSCs and cancer cells revealed that MSCs have a controversial role against cancer cells. Although some findings suggest that MSCs can reduce the growth of tumor cells, but most studies have shown an undeniable role of these cells in supporting of growth and progression of cancer. In this review article, we have accumulated some of the most important findings related to TA-MSCs and their interaction with cancer cells for immune system evation, metastasis, also their effects on the tumor cells behavior and other existing cells in TME. Lastly, we briefly explaine and classify some therapeutic solutions against tumors based on the features of MSCs.

Radiotherapy (RT) is an effective treatment in the field of cancer. Since the potential effect of RT is heavily dependent on the patient's immune system, using the immunotherapy to enhance the radiotherapy effects seems to be a positive step in the treatment of cancer.

In order to write the present review article, keywords including radiotherapy, immunotherapy, combination therapy, and immune-checkpoint inhibitors antibodies were searched in reliable databases, including Google Scholar, PubMed, Scopus, and Elsevier. Among potential candidates, those which were the most relevant to the purpose of the study and evaluated the combination of radiotherapy and immunotherapy with immune-checkpoint inhibitors antibodies were selected.

RT has distinct effects on the tumor microenvironment which can either inhibit or promote tumor growth. By inducing immunogenic cell death results in releasing danger signals, RT increases in cytokine/chemokine secretion, recruits immune cells, and alters the expression of CTLA-4, PD-1, and PD-L1 molecules on tumor and immune cells. Previous studies showed that the combination of immunotherapy and RT (radio-immunotherapy) induces the synergic effects on stimulation of anti-tumor immune response. Due to the change in the expression of immune-checkpoint molecules, including CTLA-4 and PD-1 on tumor and immune cells, and the impact on anti-tumor immune function in controlling tumor growth as a result of radiotherapy, it seems that a rational solution to overcome the inhibitory effects and to enhance the anti-tumor effects of RT is anti-checkpoint antibodies (anti-CTLA-4 and anti-PD-1). However, some factors including dose, type of radiation, and the timing of RT in relation to administration of checkpoint inhibitors are some of the challenges along this way.

Blood malignancies, one of the most common cancers in the world, cause a large number of deaths each year. Many inherited and acquired factors are involved in the development of this disease. Exosomes are a very small model of cells that are secreted by most cells in the body under physiological and pathological conditions. On the other hand, they have found a special place in the treatment of these diseases because of their very small structure and biodegradability. 

This study is a systematic review article. For this study, the electronic databases such as PubMed, Scopus and Web of Science were reviewed and 110 original and review articles were studied from 2000 to 2020. Exosome, blood malignancies and immunotherapy were used as keywords along with a number of other related terms such as tumor microenvironment, acute myeloid leukemia, acute lymphoid leukemia, chronic lymphoid leukemia and multiple myeloma (Exosome AND Leukemia, Leukemia AND Immunotherapy, Exosome AND Cancer, AML AND Exosome) to search in these databases. Finally, 51 sources that related to exosomes and myeloid and lymphoid blood malignancies were used.

The genomic profile of malignant cells and tumor microenvironment changes in the conditions of the disease. The contents of exosomes released by leukemic cells, including anti-apoptotic proteins, various microRNAs, angiogenic agents, heat shock proteins and oncogenes involved in the development of inflammatory phenotype in the target cells, are known as factors involved in the pathogenesis of leukemia. A variety of therapeutic materials such as anti-inflammatory drugs, recombinant proteins, siRNA and the inhibitor of various microRNAs can also be packaged in the exosomes with several ways and used to treat leukemia.

Exosomes derived from malignant cells play the important role in the growth and proliferation, angiogenesis, metastasis, resistance to chemotherapeutic agent, and the escape of cancer cells from the immune system by the modification of tumor microenvironment. The role of exosomes in the creation and development of blood malignancies has been proven. Therefore, using of them will probably be very helpful and promising in the treatment of these disorders with various forms.

Immunotherapy is a new strategy to prevent and treat cancers. Cancer-testis antigens has gained lots of attention as the target of anti-cancer immunotherapy. In this study, Brother of regulator of imprinted sites (BORIS) cancer-testis antigen was used to design a DNA vaccine using bioinformatics tools, and its efficacy was assessed in murine colon cancer model in Balb/C mice.

In our previous study, the immunodominant regions of the BORIS antigen were identified. They were used to design a DNA vaccine inside the pcDNA3.1 plasmid after appropriate modifications and reverse translation. The DNA vaccine was used to immunized BALB/c mice four times at weekly intervals. 14 days after the last injection, the levels of specific cytokines and antibodies were measured. Moreover, to evaluate the protective effect of the DNA vaccine, colorectal cancer cells (CT26) were injected into mice, and tumors’ growth progression evaluated for 28 days.

Vaccination with this multiepitope DNA vaccine increased the level of gamma interferon (IFN-γ) and interleukin 4 (IL-4) cytokines (P < 0.001) and specific antibodies [immunoglobulin G1 (IgG1), IgG2a, IgG total] (P < 0.001) compared to control groups [phosphate buffered saline (PBS) and pcDNA3.1-VAC]. Moreover, mean tumors volume significantly decreased (P < 0.001) in the DNA vaccine immunized group compared to control groups.

This study suggests that the use of a BORIS antigen-derived DNA vaccine can be used as a strategy to induce a significant anti-tumor immune response, and inhibit murine colon tumors growth.

Immunotherapy involves the gradual administration of increasing allergens to patients, aimed at reducing or eliminating the adverse clinical response of the patient to subsequent contact with these allergens. The aim of this study was to evaluate the effect of immunotherapy on the clinical symptoms of asthmatic patients and allergic rhinitis referred to the Allergy Clinic of Sheikh Hospital in Mashhad during 2013 to 2016. This before/after clinical trial was performed on 40 patients aged 7-50 years with mild to moderate asthma and moderate to severe allergic rhinitis. All patients had immunotherapy with allergens of pollen, weeds, and grass, based on the response of skin prick test. The effect of immunotherapy after a minimum of six months of therapy was studied. Among 40 patients with a mean age of 16.8 years, 48.1% were female and 51.9% were male. Sixty percent of patients had allergic rhinitis and 40% were asthmatics. Immunotherapy in 52.38% of patients improved daily performance and resolved sleep problems in 61.9%. Sixty-two percent of patients noted that after immunotherapy their disease was controlled easily with the drug, which was statistically significant. According to the results of this study, standard immunotherapy with inhalational allergens could be effective in reducing the clinical symptoms of patients with moderate to severe allergic rhinitis and mild to moderate persistent allergic asthma.

Cancer immunotherapy refers to any intervention that leverages the immune system to eliminate a malignancy. Successful cancer immunotherapies generate an anti-cancer response that is systemic, specific, and durable and overcome to the primary limitations of traditional cancer treatment modalities. In this review paper, the effective methods in immune system to treat cancer, such as immunosuppression in tumor microenvironment (TME), cancer vaccines and T cell adaptive therapy are mentioned. Engineered T cells can use for destruction of the different cancer tissues to diagnose tumor surface antigens. Promotion in culture of T cell methods and their engineering with retroviral vectors that carry T cell receptors or chimeric antigen receptors (CAR) by co-stimulator domains, provide opportunity to treat tumor by T cells. The tumors with high genome mutation, such as lung and melanoma, have severe environmental mutagenesis that is induced by ultra violet light in melanoma and Tobacco in lung cancers. Expression of tumor specific receptors is increased by engineered T cells. The neo-antigens conduct the intensity of intra tumor T cell response. The present of CD8+ in tumor site with more mutation is higher and the mutation load is showed strong relation with the clinical response. In addition to the successful approaches to cancer immunotherapy, the other combination and molecular therapies by nanomaterials are listed. Nanomaterials as efficient modulators and diverse vaccine have been developed in the treatment of cancer. In recent cancer vaccine development has been on subunit vaccines that contain purified tumor antigens or antigenic epitopes as an antigen source. However, soluble bolus-based subunit vaccines typically induce weak cytotoxic T lymphocyte responses which limit their utility for cancer. To overcome this, nanoscale colloids can be used to promote more efficient antigen presentation by acting as phagocytic substrates. Nanomaterials are showed co-suppression and immunization in tumor microenvironment by multiple additive functions in preclinical models. In this manner, they exhibited good prospects because of the good results in overcoming the limitations of current therapies. In this review paper is tried to provide new prospect for therapies and hope it creates highest efficacy and lowest side effects for the treatment of patients in the near future.

Cancer immunotherapy, despite its many benefits, faces major challenges. Nanoparticles are drug delivery systems that may address these challenges. The goal of this study was to produce the tumor cell lysate and Poly-IC loaded nanoparticles with desirable properties and evaluation of their therapeutic effects in mouse model of breast cancer. Nanoparticles were prepared by the double emulsion solvent-evaporation method, using poly (vinyl alcohol) (PVA) as a surfactant. Effects of molecular weight variation and the degree of hydrolyzation of PVA were investigated for the particle size, polydispersity index, encapsulation efficiency and the residual surfactant percentage of nanoparticles. 4T1 Cell line was used to induce the breast tumor in mice. To evaluate the effectiveness of the vaccine, tumor growth rate, proliferation of splenic cells by MTT assay and Delayed Type Hypersensitivity (DTH) reaction were evaluated. These results showed that the use of polyvinyl alcohol with a molecular weight of 13-23 kDa and 87-89% hydrolysis, produced nanoparticles with desirable properties. Although injection of nanoparticles containing tumor cell lysate with or without poly-IC to mice, caused a significant decrease in tumor growth, increased splenic lymphocyte proliferation, and delayed type hypersensitivity response in these two groups. But these changes, in the group that received nanoparticles containing the tumor cell lysate with Poly-IC were more significant than other groups. The results showed that the co-encapsulation of tumor cell lysate and poly-IC in one nanoparticle, due to the effects of Poly-IC on the maturation and activation of dendritic cells, enhance anti-tumor immune responses and can be considered as an effective therapeutic strategy for the treatment of breast cancer.

Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer deaths among men in the world. Immunotherapy is a new, non-invasive and effective method for the treatment of cancer, but its side effects on the normal flora of bacteria and opportunistic infections not known yet. The aim of this study was to evaluate the effects of immunotherapy on Enterococcus faecalis (E. faecalis) virulence gene expression in patients with prostate cancer. In this study, the effect of prostate cancer immunotherapy on the expression level of enterococcal surface protein (esp) gene which is involved in Enterococcus faecalis pathogenesis were investigated. For this purpose, the samples were analysed in three groups; normal individuals 211 men), prostate cancer patients (176 men) before and six months after immunotherapy period. Results showed significant (p=0.00) over expression of esp gene in prostate cancer patients after immunotherapy. There was no significant difference between prostate cancer patients before immunotherapy and healthy subjects. We conclude from these findings that immunotherapy could play a major role in increasing the pathogenicity risk of E. faecalis as a normal microflora. According to current results we suggest that using antibiotic administration in the period of immunotherapy prevents the possibility of opportunistic bacterial infections including E. faecalis.

Cancer/Testis antigens (CTAs) as a group of tumor antigens are the novel subjects for developing cancer vaccine and immunotherapy approaches. They aberrantly express in tumors with highest normal expression in testis, and limited or no expression in normal tissues. There are important similarities between the processes of germ-cell and cancer cell development Spermatogenesis begins at puberty when expression of novel cell-surface antigens occurs when the immune system has been refined the ability to distinguish self from non-self. Whereas macrophage and lymphocytes are commonly found within interstitial spaces of the testis, these antigen-presenting cells are rarely seen within the seminiferous tubules. These observations have led to the concept of the immune privileged site for testis. Localized normal expression of the CT genes in testis that makes them immunogenic for immune system, in one side, and their abnormal expression in different kinds of cancer cells, in the other side, has make them as promising target for developing cancer vaccines and new cancer therapeutics approaches. In malignancies, gene regulation is disrupted which results aberrant expression of CT antigen in a proportion of tumors of various types. For some CTAs, data support their fundamental role in tumorigenesis. Several authors believe it is not clear whether they have an essential role in tumorigenesis or they are by-products of chromatin variations in cancer. There is a growing list of CTAs within them advanced clinical trials are running by using some of them in cancers like lung cancer, malignant melanoma and neuroblastoma. In this review we discuss the gene TSGA10 as an example of CT genes. TSGA10 expresses in its highest levels in elongating spermatids and localized in the fibrous sheath of mature sperm. This gene is proposed as a serological biomarker in cutaneous lymphoma. Its abnormal expression has been reported in different cancers such as acute lymphoblastic leukemia, breast, brain, gastrointestinal and a range of other cancers either in mRNA or protein levels. It has an important role in angiogenesis in cancer tumors because of its effects in the gene hypoxia-inducible factor (HIF1). Absence or lack of TSGA10 expression has been reported in ascosporic infertile men.

Breast cancer, assumed as a difficult -to –treat disorder across the world, is the most common malignancy among women. Over decades, significant advances in breast cancer immunotherapy and tumor immune biology have been brought about. In vitro studies of the effect of various cytokines have been conducted in breast tumor. Among Interleukins, IL-27 -a novel cytokine- is associated with specific properties. Moreover, IL-27 contributes to the Th1 induction and also acts as a pro- inflammatory cytokine. The aim of this study was to evaluate the IL-27 anti-proliferative effects on 4T1 cell line in vitro.

In this study, 4T1 cells were cultured in RPMI1640. mIL-27 gene was cloned, cells were transfected and recombinant protein was produced. Then, anti-proliferative effect of IL-27 on 4T1 breast cancer cell line was evaluated.

Our results indicated that IL-27 could suppress 4T1 cell proliferation significantly (p<0/01). Cell to cell interactions and also morphology of the cells were remarkably changed in comparison to control cells.

Our results showed that, IL-27 under in vitro conditions, could potentially suppress tumor without any essential cells and biologic factors of tumor matrix. Therefore, rmIL-27 may be a probable candidate protein as an antitumor agent, applicable to breast cancer immunotherapy.

Allergen immunotherapy involves the administration of gradually increasing quantities of specific allergens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure. This study evaluated the clinical efficacy of immunotherapy with extracts of common aeroallergens North-East of Iran in asthma and allergic rhinitis. In this prospective study 156 cases were chosen randomley. The mean age of patients was 37 years (range 5-65 years). The patients with mild to moderate asthma and allergic rhinitis and history of atopy were selected for immunotherapy when they showed no effective response to medical treatment. Immunotherapy materials were made from common aeroallergens in north-eastern region of Iran by Dome Hollister US company. Immunotherapy schedule for injection of the extract with vial dilution of 1:10000pg was one injection every week for ten weeks and one injection with dilution of 1:1000pg every other week for the other ten weeks and one injection monthly from dilution of 1:100pg for two years. One hundred twenty (77%) of cases had allergic rhinitis 29 (18. 5%) cases had allergic asthma and 7 (4. 5%) cases were mixed. Mean age of patients were 37 years old. 48 (30. 8%) cases were male. Analysis of efficacy of treatment showed that immunotherapy significantlyimproved the signs and symptoms of all the groups. In allergic rhinitis group 84 (70%) cases completely improved، 22 (18. 4%) patients moderately responded and no response to immunotherapy was observed in 14 (11. 6%) patients. In allergic asthma group، 22 (75%) cases completely improved 4 (13. 6%) cases moderately responded and no response to immunotherapy was detected in 3 (11. 4%) cases. In mixed group، 3 (42. 8%) cases completely improved، 3 (42. 8%) cases moderately responded and no response was observed in 1 (14. 4%) case. Specific allergen immunotherapy for patients with allergic persistent mild to moderate asthma and moderate to severe allergic rhinitis without good response to medical treatment is highly recommended. It is recommended as effective treatment in such patients.

Dendritic cells are the most potent antigen presenting cells in induction or polarization of T-dependent immune responses. In cancerous patients, suppressive or detoured immune responses regard to tumor cells, prevent appropriate functions of dendritic cells. Nowadays, in vitro production, expansion and maturation of dendritic cells in presence of safe maturation factors which polarize TH1 responses in donors, is the base of many cancer immunotherapy studies. The aim of this study was to evaluate the effect of melphalan-induced damaged DNA on dendritic cell maturation, phenotypes and its induced immune responses in T helper cells related to improvement or aggravation of the disease. In this study, we analyzed the effect of MCF-7 derived damaged DNA (Induced by melphalan alkylating agent) in addition to standard maturation factors (TNF-α and MCM) on maturity characters of dendritic cells consisting of morphology, phenotype, phagocytosis, MLR, and cytokine secretion compared with the control group. The data showed that the combination of damaged DNA with standard maturation factors in treatment of dendritic cells result to an increased expression in CD83 (the marker of matured DC) and a decreased levels of phagocytosis. Besides, damaged DNA polarized immune responses to DC1 phenotype triggering TH1 responses. Results demonstrate the efficiency of damaged DNA in induction of mature dendritic cells and their appropriate immune responses against MCF-7 cell line.

Background and ObjectivesThe specific activation of the immune system especially T lymphocytes has been a long-term goal of cancer immunotherapy. In an approach to induce the patient’s own immune cells, chimeric antigen receptors (CAR) were used to activate cytotoxic T lymphocytes. The CAR consists of an antigen binding domain of antibody molecule linked through an extracellular linker to transmembrane and cytoplasmic domains of lymphocyte-triggering moieties. Materials and MethodsIn our research group, variable domains of heavy chain antibodies (VHH or nanobody) derived from camelids were used instead of the antigen-binding domain in chimeric receptors constructs. To obtain a stable and increased expression of VHH harboring CAR, the PhiC31 integrase system was used for CAR gene integration into the T-cell genome. Constructs expressing CAR and PhiC31 integrase were co-transfected into the Jurkat cell line and CAR expression was quantified after one day and 30 days after transfection by a semi-quantitative RT-PCR method. ResultsOur results on day 30 confirmed that co-transfection of PhiC31 integrase constructs and CAR expressing constructs resulted in stable and high expression of the receptors. ConclusionsBased on our results, we conclude that PhiC31 integrase enzyme can be used for immunotherapy of cancer mediated by T cells expressing chimeric recetors.

Using dendritic cells (DCs) loaded with tumor antigens as a therapeutic strategy against tumors has been proposed. In order to increase the efficacy of DCs، a variety of factors such as TLR ligand molecules and bacterial products are used. In this study، the protein components of the bacteria Listeria monocytogeneses (LM) for induction of dendritic cell maturation were used. Bone marrow cells of Balb/c mice in the presence of IL-4 and GM-CSF were cultured for 5 days. On day 5، tumor lysate and then protein components or total extract of LM was added to immature DCs. In order to survey the maturation status of DCs، on day 7، the expression of CD80، CD86 AND MHC-II on the cell surface was evaluated. After induction of tumors in mice using WEHI-164 cell line، 106 mature dendritic cells subcutaneously injected. Tumor growth rate، survival rate and cytotoxic activity of spleen cells were evaluated in the studied groups. In mice vaccinated with protein components matured-DCs، delayed tumor growth rate and increased survival were seen. In addition، in these mice، the cytotoxic activity of spleen cells was higher compared to other groups. In all groups receiving protein components or total extract mature-DCs، increased cytotoxic activity and decreased tumor growth rate were seen compared to controls. Listeria monocytogenes protein components compared to total extract have higher ability to increase the efficacy of DCs for tumor immunotherapy in mouse model.

Background and In spite of the increasing progress in tumor treatment by current methods like surgery, chemotherapy and etc, medical sciences are unable to treat tumors. In this respect, immunology has opened a new window for tumor treatment nowadays tumor immunotherapy is an accepted strategy for treatment of some tumors at least in some animal models. The goal of this study is the evaluation of immunotherapy using gp96- tumor peptide complex and its combination with naloxon as an opioid receptor antagonist to achieve of cellular immunity against tumors In this study firstly, gp96 – tumor peptide complexes were purified from WEHI164 cells line using srivastava method. In the next stage, the mice, made tumoric befor by the injection of tumor cells, then were divided in to four groups. Control group were injected by PBS, test group1 were injected by naloxon, test group2 were injected by gp96 – tumor peptide complex and test group3 were injected by combination of naloxon and gp96 – tumor peptide complex. To evaluation the efficacy of vaccination, after several days, tumor volume was recorded then the mice were killed and the spleanic cells were extracted in sterile condition. MTT test was done for cells proliferation study. Supernatant of cultured cells were collected and assayed by ELISA kits for measuring IL-4 and IFN-γ. Result of protein purification had showen, purified gp96 Isoform has Molecular Weight of 66 kilo dalton.Results of tumor volume had shown that, there is no significant difference between test and control groups. Results of MTT test had shown that, there is no significant difference between test and control groups. IL-4 assay study had showed that, there is no significant difference between test group1, group2 and control group but test group3 has significantly decreased in IL-4 amount when compared with control group. Results of IFN-γ assay showed that, there is no significant difference between test group1 and control group, but test group2 and group3 has significantly increased in IFN-γ amount when compared with control group. It can be concluded from this study is that, prophylactic immunotherapy of tumor by combination of gp96-tumor peptide complex and naloxon, can increase IFN-γ, and, probably in a higher dosage, it may stimulate immune system more to become more potent to even decrease tumor volume.

Bladder cancer is the second common genitourinary tract cancer in the world.Immunotherapy with intravesical Mycobacterium bovis BCG is the selective treatment for superficial bladder cancer. CD/5FC Enzyme-Prodrug system of gene therapy is an alternative technique for controlling bladder cancer. This research is aimed at the design and construction of mycobacterial shuttle vector containing hsp60 promoter, alpha antigen signal sequence and cytosine deaminase (CD) and consequent transformation to M.bovis BCG by electroporation. It is assumed that converting of 5-FC to 5-FU via CD will kill more tumor cells and increase the efficacy of this therapeutic method. After amplification of mycobacterial shuttle vector gene fragments containing hsp60 promoter, alpha antigen signal sequence and Saccharomyces cerevisiae CD gene by PCR and enzymatic digestion, they were cloned and subcloned in pBGGT and pVN2 respectively. The final plasmid was transformed to M. bovis BCG by electroporation method. Sequencing results confirmed the integrity and correctness of final vector which called pHARA. The cells which received pHARA, were cultured on Middlebrook 7H10 agar with 20μg/ml final concentration of kanamycin, and grown during 17 days. Mentioned recombinant BCG (rBCG) secreting CD enzyme in addition to adjuvant property and stimulation of local immunity responses against tumor cells, can also destroy more tumor cells through converting 5-FC to 5-FU via CD enzyme that intensifies BCG efficacy in treatment of superficial bladder cancer.

Treatment of resistant warts is a common clinical problem. Immunotherapy with diphenyl cyclopropenone (DCP) as a contact sensitizer has been reported. The objective of this study was to evaluate the efficacy of DCP in refractory warts.

Nineteen patients with refractory warts referred to Razi Hospital in 2004 who had not responded to at least 2 treatment modalities, were sensitized with 2% DCP in acetone. Then treatment was started with application of 1% DCP on plantar warts and 0.2% on other locations.

Two patients were not sensitized even after 3 attempts. Three other patients discontinued treatment due to side effects (severe eczema and pruritus). Six male and 8 female patients completed the trial, among them, 10 (71.5%) showed complete clearance of warts. Side effects reported were: local pruritus (21%), distant eczema (10.5%), local blister (26.3%). The patients received a mean of 5 treatment sessions.

Topical immunotherapy with DCP is an effective treatment for refractory warts. Due to high efficacy, no scarring, and being a painless procedure it can be considered as a first line treatment of refractory warts.