Cancer metastasis, the spread of disease from a primary to a distal site through the circulatory or lymphatic systems, accounts for over 90% of all cancer related deaths. Despite significant progress in the field of cancer therapy in recent years, mortality rates remain dramatically higher for patients with metastatic disease versus those with local or regional disease. Although there is clearly an urgent need to develop drugs that inhibit cancer spread, the overwhelming majority of anticancer therapies that have been developed to date are designed to inhibit tumor growth but fail to address the key stages of the metastatic process: invasion, intravasation, circulation, extravasation, and colonization. There is growing interest in engineering targeted therapeutics, such as antibody drugs, that inhibit various steps in the metastatic cascade. We present an overview of antibody therapeutic approaches, both in the pipeline and in the clinic, that disrupt the essential mechanisms that underlie cancer metastasis. These therapies include classes of antibodies that indirectly target metastasis, including anti‐integrin, anticadherin, and immune checkpoint blocking antibodies, as well as monoclonal and bispecific antibodies that are specifically designed to interrupt disease dissemination. Although few antimetastatic antibodies have achieved clinical success to date, there are many promising candidates in various stages of development, and novel targets and approaches are constantly emerging. Collectively, these efforts will enrich our understanding of the molecular drivers of metastasis, and the new strategies that arise promise to have a profound impact on the future of cancer therapeutic development. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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Our results suggest that the callosal shape deformation patterns, especially those of sCC, linked tightly to the cognitive decline in AD, and are potentially a powerful biomarker for monitoring the progression of AD.

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Mitochondrial shape changes are essential to mitochondrial functions. Quantification of mitochondrial shape changes is essential to understanding related physiology and disease mechanisms. In this study, we proposed a new automated pipeline for quantifying the shape changing patterns of mitochondria in the framework of large deformation diffeomorphic metric mapping for curve. We validated the accuracy of our pipeline on 32 mitochondria data, each having 6 sequential time-lapse frames. The contour of each mitochondrion is modeled by a curve consisting of a set of landmark points ranging from 39 to 358, with the moving distance between every two consecutive frames quantified for each localized point. The sensitivity of the proposed pipeline, with respect to different curve discretization, was investigated, with high robustness established. In addition, we quantified the uncertainty level of the proposed pipeline using 10 fixed mitochondria data with 6 time frames as well, with the mean between-frame moving distance found to be smaller than 28 nm for a majority of the 10 fixed mitochondria data. This indicates that the proposed pipeline has a very low level of uncertainty. The encouraging results from this work suggest that the proposed pipeline is potentially a powerful tool for quantifying shape dynamics, both globally and locally, of a variety of cellular components.

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Acute myeloid leukemia (AML) is a highly prevalent blood and bone marrow cancer characterized by the uncontrolled growth of abnormal myeloblasts. Current treatments for AML often result in systemic toxicities for patients, many of whom will still experience relapse. There is thus an unmet need to develop safer and more effective therapies targeting AML. Chimeric antigen receptor (CAR) T cells, which are engineered to express a cancer-targeting extracellular antibody single-chain variable fragment (scFv) linked to an intracellular T cell-activating domain, have shown promise in treating B cell leukemias, but their success has been limited in myeloid leukemias. This is due in part to the lack of AML-specific target antigens. Moreover, impaired T cell function, a hallmark of AML, is also problematic when relying on autologous T cell activation upon reinfusion. We overcame the limitations of CAR T therapy in AML by developing CAR-expressing natural killer (NK) cells targeting CD123. While present on both healthy and AML cells, CD123 is expressed at >10-fold higher levels on malignant cells. Furthermore, use of NK cells allows use of fully functional allogeneic cells from healthy donors, since NK cells do not induce graft-versus-host-disease. To optimize the tumor cell selectivity of CAR NK cells, we employed the yeast display directed evolution platform to isolate anti-CD123 scFvs with varying affinities and are identifying clones that maximize the interaction with CD123high AML cells over healthy CD123low cells, as determined by binding, cytotoxicity, and cytokine secretion studies. Collectively, our efforts introduce a new paradigm for engineered cell therapeutics with significant promise for AML treatment.