Randomized,controlled, double-blinded field trial to assess Leishmania vaccine effectiveness as immunotherapy for canine leishmaniosis

Better tools are necessary to eliminate visceral leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic leishmaniasis. We performed a double-blinded, block-randomized, placebo-controlled, vaccine immunotherapy trial testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted, vaccine, LeishTec®, in owned hunting dogs infected with L. infantum. The primary outcome was reduction of clinical progression, with reduction of mortality as a secondary outcome. Vaccination as an immunotherapy reduced the risk of progression to clinically overt leishmaniasis by 25% in asymptomatic dogs (RR: 1.33 95% C.I. 1.009–1.786 p-value: 0.0450). Receiving vaccine vs. placebo reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95% C.I.: 1.185–8.502 p-value = 0.0245). Vaccination of infected-healthy animals with an anti-Leishmania vaccine significantly reduced clinical progression and decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be a tool for Leishmania control.     

Monoclonal Antibodies in Multiple Myeloma: A New Wave of the Future

In 2015, 2 monoclonal antibodies were approved for the treatment of relapsed or refractory multiple myeloma (RRMM), elotuzumab and daratumumab. Elotuzumab is a monoclonal IgG-κ antibody directed against SLAMF7 (signaling lymphocytic activation molecule F7), a cell surface receptor involved in natural killer cell activation. Daratumumab is a monoclonal IgG-κ antibody that binds to CD38, a transmembrane protein found on the surface of myeloma cells and responsible for cellular adhesion and ectoenzymatic activity. Both elotuzumab and daratumumab act through recruitment of the immune system to enhance cellular cytotoxicity directed against myeloma cells. Elotuzumab requires lenalidomide and dexamethasone combined to enhance progression-free survival in patients with RRMM, and daratumumab has both single-agent and combination activity with either lenalidomide or the proteasome inhibitor bortezomib in RRMM. The adverse effect profile of both agents mainly consists of allergic-type infusion reactions. Other considerations for monoclonal antibody use in the treatment of MM include the potential for interference in serum protein electrophoresis testing and cross-reactivity of daratumumab with CD38 present on red blood cells. In the present report, we discussed the clinical development of daratumumab and elotuzumab and newer immunologic approaches to the treatment of MM.     

Precision Medicine in Myeloma: Challenges in Defining an Actionable Approach

Recently, large sequencing studies have provided insights into the mutational landscape of multiple myeloma (MM), identifying actionable mutations and giving a precious opportunity for exploring new targeted therapies. The main goal of precision medicine, matching patients with the right drug, seems to be closer than ever. However, no targeted therapies in MM are approved yet. Several clinical trials testing targeted drugs and enrolling patients with MM are currently ongoing and will provide predictive biomarkers that might support clinical decision making. In this review, we evaluate the evidence supporting the implementation of precision medicine in MM and we discuss the challenges that should be dealt with in this imminent and promising new era.     

Blocking “don't eat me” signal of CD47-SIRPα in hematological malignancies,an in-depth review

Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. Hu5F9-G4, a humanized anti-CD47 blocking antibody is currently being studied in four different Phase I trials. These studies may lay the groundwork for therapeutic bispecific antibodies. Bispecific antibody (CD20-CD47SL) fusion of anti-CD20 (Rituximab) and anti-CD47 also demonstrated a synergistic effect against lymphoma in preclinical models. This review summarizes the large body of preclinical evidence and emerging clinical data supporting the use of antibodies designed to target the CD47-SIRPα interaction in leukemia, lymphoma and multiple myeloma.     

B7-H5在乳腺癌中的表达及其临床意义

目的研究乳腺癌中B7 H5的表达及其临床意义。方法收集2020年6月至2021年4月苏州大学附属第一医院48例乳腺癌患者的癌组织、正常乳腺组织及血液标本，进行流式细胞学分析B7 H5表达。整理并分析了相关临床数据及病理特征。使用Kaplan Meier绘图仪数据库，对B7 H5不同表达程度的乳腺癌患者进行预后分析。结果乳腺癌组织中的B7 H5表达高于正常乳腺组织（P<0001）；B7 H5的表达与患者淋巴结转移情况及乳腺癌TNM分期呈负相关。Kaplan Meier绘图仪数据库分析显示，B7 H5 mRNA高表达乳腺癌患者的生存率高于低表达者（P=0019）；B7 H5高表达组的根治性治疗到复发的时间(RFS)明显高于低表达组（P<0001）。结论B7 H5在乳腺癌组织中显著高表达，其与乳腺癌患者疾病预后相关，B7 H5高表达预示着较好的预后及生存期。     

Progress in Novel Cellular Therapy Options for Chronic Lymphocytic Leukemia: The MD Anderson Perspective

Over the past several years there has been considerable progress in the number and breadth of therapeutic options for patients with chronic lymphocytic leukemia. In particular, cumulative experience with stem cell transplant and immunotherapy has made these modalities more available to a broader range of patients. Advances in genetic engineering and ex vivo expansion techniques have sculpted cellular therapy products to optimize the combination of specificity and toxicity. This brief review discusses recent cutting-edge experience with chimeric antigen receptor T cells as well as developing cellular therapy products at the authors' institution.     

雄激素剥夺疗法和免疫疗法在前列腺癌治疗中的研究进展

前列腺癌在美国成年男性中发病率位居第一，癌症相关致死率位居第二。雄激素剥夺治疗是最常用的前列腺癌治疗方法，而且通常伴随患者的终身治疗。雄激素和雄激素剥夺疗法对免疫系统有着重要的影响，在目前免疫治疗受到持续关注的情况下这一发现显得尤为重要。研究表明，雄激素剥夺治疗可能对免疫治疗起到促进或者抑制的作用。本文综述了不同类型雄激素剥夺治疗药物的作用机制，探讨了其对前列腺癌细胞及患者免疫系统的影响，以及联合使用雄激素剥夺药物和免疫治疗的前景，为前列腺癌的治疗提供了新的视野和思路。     

NK cell-based immunotherapy for cancer

Natural killer (NK) cells can induce an antigen-independent immune response against malignant cells. A growing number of scientific reports and clinical studies have shown promising anti-tumor effects when using NK cell-based immunotherapy. Currently, various approaches are being used to enhance the number and function of NK cells. One approach uses cytokines to selectively boost both the number as well as the efficacy of anti-tumor functions of NK cells. Another emerging approach focuses on checkpoint inhibitors targeting the NK cell receptor. Furthermore, bi-specific and tri-specific engagers have been developed to enhance the specific immune response by cross-linking specific tumor antigens to effector cells. In addition, NK cell adoptive transfer therapies have shown promising prospects. Among the various sources of adoptive transfer NK cells, allogeneic haploidentical NK cells that have undergone short- or long-term activation or expansion have also demonstrated effective anti-tumor effects with a low rate of rejection and side effects. CAR-NKs, derived from a new type of genetic modification, show enhanced NK cell cytotoxicity, specificity, and targeting. These NK cell-based therapies have exhibited promising results in clinical trials with malignant tumors. In this review, the current progress on NK cell-based therapeutic approaches, NK cell manufacturing techniques and tumor therapy outcomes are discussed.