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Background : Poly(I:C) is a Toll-like receptors 3 agonist, which induces potent innate immune responses, and as a consequence adaptive immunity. However, the rapid degradation of poly(I:C) influences its half-life and its adjuvant effects in preclinical and clinical uses. Aims : We aimed in this study to conjugate poly(I:C) with polyethylene glycol/poly D, L-actide-co-glycolide (PLGA/PEG) polymers as an approach for better delivery and immunomodulatory effects. Materials and Methods : Female CD1 mice were treated once with PEG/PLGA, poly(I:C)/PLGA/PEG (50 μg), poly(I:C)/ PLGA/PEG (10 μg) or PEG via intraperitoneal injection and mice were sacrificed 1 day later for complete blood count analysis and analysis of the immune cells by flow cytometry. Results : Treatment with PEG/PLGA, poly(I:C)/PLGA/PEG (50 μg), poly(I:C)/PLGA/PEG (10 μg) or PEG administration resulted in significant (P = 0.0197) increases (1.89, 1.76, 1.69, and 1.42-fold, respectively) in the absolute number of neutrophils as compared to naive mice. Conclusion : Conjugation of poly(I:C) with polymers does not hamper its immunomodulatory effects, instead it enhances its effects on increasing the number of immune cells opening an avenue for further studies on the beneficial effects of this conjugate.

Background: Integrating immunotherapy and chemotherapy is most likely to be the basis for new optimism in targeting cancer therapies to form local tumor microenvironment and attack tumors early in their development. This regimen has some potential risks such as myelo- and immunosuppression and chemo-resistant tumor cells. Aim: The present study aimed to investigate the combination of chemotherapy, immunotherapy, and the prospective of mobilized stem cells for optimization and modulation of the immune system to overcome immunosuppression and kill distant cancer cells. Materials and Methods: Ehrlich ascetic carcinoma (EAC) cell line-bearing mice treated with cyclophosphamide (CTX) followed by adoptively transferred with in vitro -activated T-cells either harvested from naive or EAC-bearing host with or without unfractionated bone marrow (BM) cells or granulocyte-colony stimulating factor-mobilized hematopoietic stem cells (HSCs) 1-day post-CTX treatment. All mice were vaccinated with EAC lysate and Hiltonol. Results: Cotransfer of activated T-cells obtained from EAC-bearing mice with HSC-progenitors induced the highest antitumor effect through increasing the percentage of apoptosis and decreasing DNA replication in S phase of EAC cells. Besides, marked an increase in the percentage of myeloid cells in spleen and stem cell populations in BM cells. Interestingly, Adoptive T-cell transfer (ACT) derived from EAC-bearing host with or without BM cells induced mobilization of stem cells from BM to circulation increasing their expansion. Conclusion: Combination of chemotherapy with ACT plus vaccination may constitute a potent antitumor therapy that provides more efficacious antitumor responses when it is combined with BM cells fostering more effective antitumor immunotherapy strategies.

Background: Granulocyte colony stimulating factor (G-CSF) is used in clinical practice to mobilize neutrophils alone or in combination with chemotherapy. However, its influence in physiological indices has not been addressed well in certain animal models such as Wistar rats. Aims: To evaluate the single and combinatorial effects of G-CSF and cyclophosphamide (CTX) on physiological indices in Wistar rat. Materials and Methods : Naive female Wistar rats were treated with subcutaneous injection of pharmaceutical benefits scheme, (5 μL/day/rat) G-CSF for 5 consecutive days and single intraperitoneal injection of CTX (4 mg/rat). Body weights were obtained daily. Rats were sacrificed 1-day after the last injection to obtain different organ weight and to analyze the physiological indices in plasma and the liver. Results: G-CSF alone induced increases in body weight, splenomegaly, white blood cells, platelets, and alanine aminotransferase (ALT) activity. It, however, decreased neutrophils and monocytes, aspartate aminotransferase (AST) activity, red blood cells and hemoglobin level. CTX alone induced decreases in body weight, white blood cells, neutrophils, red blood cells and hemoglobin level. It, however, increased spleen weight, lymphocytes, monocytes, ALT activity and AST. G-CSF + CTX induced increases in body weight, splenomegaly, lymphocytes and ALT. It, however, decreased white blood cells, platelets number, neutrophils, monocytes, red blood cells and hemoglobin level. Conclusion : Among different physiological indices, treatment with single or combinatorial G-CSF increases the total number of white blood cells in Wistar rats which need to be considered while using this model animal disease.

Background: Acute lymphoblastic leukemia (ALL) is considered as one of the most common cancer in pediatric malignancies. Among ALL, B-cell Acute Lymphoblastic Leukemia (B-ALL) represents 80% to 85% of the childhood ALL. Problem: Although anti B-ALL chemotherapy kill B-ALL, it associates with alteration in the numbers of CD4+ and CD8+ T-cells, and thus impacts the overall immunity. Aim: To evaluate the impact of anti B-ALL on the numbers of CD4+ and CD8+ T-cells in correlation to the numbers of CD10+ B cells in B-ALL pediatric patients. Materials and Methods: Peripheral blood samples were drawn from previously diagnosed B-ALL before (n = 10 cases) and after (n = 10 cases) chemotherapy as well as from healthy controls (n = 10 cases). The numbers of CD4+, CD8+ T-cells and CD10+ B cells were measured in these samples by flow cytometry. Results: As expected, the numbers of CD10+ B-cells were increased in B-ALL patients before chemotherapy which were associated with increases in the numbers of CD4+ and CD8+ T-cells. Chemotherapy of B-ALL patients, during the induction phase, induced dramatic decreases in the numbers of CD10+ B cells, which were associated with decreases in the numbers of CD4+ and CD8+ T-cells. Tin spite of this alteration, the ratio of CD4/CD8 in B-ALL patients were remained similar before and after chemotherapy as compared to those in healthy controls. Conclusion: Anti B-ALL chemotherapy induces alterations in the frequencies of T-cell subsets. Given the importance of these cells in anti-tumor immunity, our data may lead to further studies to investigate the different subsets of these cells, in particular regulatory T-cells.

Background: Acute lymphoblastic leukemia (ALL) is biologically and clinically considered as a heterogeneous neoplasm of lymphoid progenitor cells. About 85% of children with ALL are diagnosed as B-ALL, expressing CD19; the typical marker of normal B cells. Problem: Given that the chemotherapy associated with leucopenia, in particular myeloid cells (CD33+ cells), Aim: the main aim of this study was to analyze the numbers of these cells in children with B-ALL before and after induction of chemotherapy. Materials and Methods: The frequencies of CD33+ myeloid cells and CD19+ B-cells were analyzed in the peripheral blood patients before (n = 10) and after (n = 10) induction of chemotherapy as well as in healthy volunteers (n = 10) using multiparametric flow cytometry. Results: As expected, B-ALL patients showed high numbers of CD19+ cells before induction of chemotherapy; where the numbers of these cells were reduced upon the induction of chemotherapy. CD33+ myeloid cells showed decrease in numbers in B-ALL patients before chemotherapy as compared to healthy control volunteers. Interestingly, treatment of B-ALL patients with chemotherapy-induced almost recovery of the numbers of these cells. Conclusion: CD33+ myeloid cells are increased in numbers after induction of chemotherapy, indicating to a dynamic mobilization or differentiation of their precursors into circulation. This study opens a new avenue to characterize the phenotype and function of these cells in different hematological malignancies; in particular, they may harbor regulatory cells.