Highlight The emergence of CAR-T cell therapy with its exciting results attained in patients with relapsed and refractory hematological malignancies is considered as the biggest advance in cellular cancer immunotherapy. However, severe side effects and toxicity stir concerns regarding the safety of CAR-T cell treatments.Most of CAR-T cell therapies are currently autologous small-scale treatments for patients suffering from B cell malignancies due to the safety concerns about the potential development of a GVHD in allogeneic therapies. So, allogeneic therapies have been less effective than autologous ones. High cost and highly variable manufacturing processes are other limitations on the way of CAR-T cell therapy. In contrast to the unprecedented responses achieved through using CD19-CAR-T cells in the treatment of ALL, this type of treatment has not shown the same results in the battle against solid tumors that is partly related to different characteristics and microenvironment of solid tumors that limit the success of CAR-T cell therapies in patients with solid tumors. Immune checkpoint therapies with previously reported reproducible beneficial effects in 20–30% of patients with different incurable cancers have serious side effects and considerable cost of repeated administration. Also, recently most patients have not responded effectively to these therapies. In contrast, CAR-T cell therapy has two characteristics that may compensate for the limitations of immune checkpoint therapies. Firstly, only one administration of the engineered T cells is needed for long lasting effectiveness of the therapy. Secondly, more than 90% of patients suffering from ALL respond to CAR-T cell therapy, a result which is not obtained through administration of the immune checkpoints. Future development of CAR-T cell technology should address concerns related to the safety of the treatment and improve toxicity management. Also, it should extend the application of technology in diseases where its effectiveness has been demonstrated and opt for more targets and cancers.

HighlightsIn this study, two immunogenic antigens based on recombinant PspA proteins were immunized mice.The protective effects of developed anti-PspA antibodies in mice in intranasal and intraperitoneal challenges were proved.Based on the obtained results, immunization with the B-regions of PspA antigens are crucial in protection of challenged mice with S. pneumoniae strains.

Acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) are common acute leukemia in adults and children, respectively. In these malignancies, chemotherapy is the main treatment strategy that fails in many cases and is usually associated with adverse effects on healthy cells. In this regard, the development of new therapies is essential. Monoclonal antibodies directed to the cell surface markers of leukemic blasts may have promising consequences with minimal toxic effects on normal cells. Since cluster of differentiation 45Ra (CD45Ra) and CD123 antigens, two considered surface markers of leukemic blasts in AML and ALL respectively, are overexpressed on AML and ALL blasts, CD34+ leukemic progenitors, and AML-LSCs in comparison with normal hematopoietic stem cells (HSCs), they were selected to be targeted; using specific monoclonal antibodies. In this project, CD45Ra+ cells and CD123+ cells were targeted by anti-CD45Ra and/or anti-CD123 monoclonal antibodies. Cytotoxicity effect and cell death induction was determined by 3-(4,5-dimethylthiazol-2-yl)-2–5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Changes in the expression profile of MCL1, cMyc, Survivin, Id1, and PIM1 genes were assessed by real-time PCR. Statistical analysis of the results showed effective antibody-mediated cytotoxicity and induction of apoptosis in KG1α (CD45Ra+) and Nalm6 (CD123+) cell lines. Also, a significant change in the expression level of some of the apoptosis-related genes was observed. According to the results of this study, it can be concluded that an effective targeting of AML and ALL cancerous cell lines can be performed by anti-CD45Ra and anti-CD123 monoclonal antibodies through their effector functions and apoptosis induction.