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Background: Since numerous chemotherapy regimens for the treatment of patients suffering from acute lymphoid leukemia (ALL) have been recently developed, having basic information about the previous results of using the Hyper-CVAD regimen in order to compare with other common chemotherapy regimens is essential. The aim of this study was to evaluate demographic, clinical and outcome of ALL patients receiving Hyper-CVAD regimen. Methods: In this retrospective study, nighty eligible ALL patients treated with the Hyper-CVAD chemotherapy regimen in Omid Hospital, Isfahan, Iran during April 2016 till April 2019 were considered. We evaluated the demographic variables, pathological data and other clinical factors by an information sheet designed by main investigator. The main purpose of this study was to evaluate overall survival, progression-free survival, and overall response rate of patients along with patients’ clinical characteristics and other relevant factors using Kaplan-Meier or Cox-regression and other statistical analyses. Results: The mean overall survival and the median survival of patients were 44.8±2.93 and 36.7±7.47 months; respectively. Also the mean progression free survival of patients was 44.44±3.30 months. More than 84.4% of patients encountered complete remission (CR) after receiving Hyper-CVAD regimen. Reaching to CR had positive significant effects on patients’ overall survival and median survival. However, the bone marrow transplantation variable alone did not affect the patients’ overall survival. The variables such as being B/T Cell ALL, Philadelphia, myeloid marker, and central nervous system involvement did not affect the overall survival of patients but the relapse index indicated the significant effects. The median survival time is higher in patients with no relapse episode. None of the initial lab data had any significant effects on patients’ overall survival. Conclusion: For the first time in Iran, we have obtained the mean survival outcome of ALL patients after applying the Hyper-CVAD regimen. According to the results, the mean overall survival, progression free survival and other survival items in Iranian patients suffering from ALL and receiving Hyper-CVAD regimen were in consistent with previous studies in the world.

Background: Immune checkpoints are molecules that act as regulators of immune system pathways. However, some tumor cells can express the ligands of immune checkpoints to escape from antitumor immune responses. Some agents, such as antibodies, can inhibit these checkpoints that prevent the immune system from targeting and killing cancer cells. The aim of this study was to express a novel bispecific tandem scFv in periplasmic space of Escherichia coli for simultaneous targeting of two immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Materials and Methods: The bispecific tandem scFv was constructed based on the variable regions gene of anti-PD1 and anti-CTLA-4 antibodies. The optimum codon for expression in E. coli was chemically synthesized and subcloned in periplasmic expression plasmid. After transformation, the effect of cultivation conditions on periplasmic expression of the protein in E. coli BL21(DE3) was evaluated. Then, the bispecific tandem scFv was purified and its binding ability to cells expressing PD-1 and CTLA-4 was evaluated. Results: Expression of tandem scFv with a molecular weight of 55 kDa was verified by Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting analysis. The best condition for soluble periplasmic expression was obtained to be incubation with 0.5 mM isopropyl β-D-1-thiogalactopyranoside at 23°C. The protein was successfully purified using affinity chromatography with a final yield of 4.5 mg/L. Binding analysis confirmed the bioactivity of purified the tandem scFv. Conclusion: This bispecific tandem scFv could be a potential candidate to cancer immunotherapy, although more biological activity assessments are still required to be carried out.