Antibody dependent cell-mediated cytotoxicity selection pressure induces diverse mechanisms of resistance.

Targeted monoclonal antibody therapy has emerged as a powerful therapeutic strategy for cancer. However, only a minority of patients have durable responses and the development of resistance remains a major clinical obstacle. Antibody-dependent cell-mediated cytotoxicity (ADCC) represents a crucial therapeutic mechanism of action; however, few studies have explored ADCC resistance.

Targeting Immunosuppressive Adenosine Signaling: A Review of Potential Immunotherapy Combination Strategies.

The tumor microenvironment regulates many aspects of cancer progression and anti-tumor immunity. Cancer cells employ a variety of immunosuppressive mechanisms to dampen immune cell function in the tumor microenvironment. While immunotherapies that target these mechanisms, such as immune checkpoint blockade, have had notable clinical success, resistance is common, and there is an urgent need to identify additional targets.

The Next Generation of Cellular Immunotherapy: Chimeric Antigen Receptor-Natural Killer Cells.

The advent of chimeric antigen receptor (CAR) engineering has led to the development of powerful cellular therapies for cancer. CAR T cell-based treatments have had notable clinical success, but logistical issues and associated toxicities are recognized limitations. There is emerging interest in using other immune effector cell types for CAR therapy.

Monoclonal Antibodies in Cancer Therapy.

Monoclonal antibody-based immunotherapy is now considered to be a main component of cancer therapy, alongside surgery, radiation, and chemotherapy. Monoclonal antibodies possess a diverse set of clinically relevant mechanisms of action. In addition, antibodies can directly target tumor cells while simultaneously promoting the induction of long-lasting anti-tumor immune responses.

Overcoming malignant cell-based mechanisms of resistance to immune checkpoint blockade antibodies.

Traditional cancer treatment approaches have focused on surgery, radiation therapy, and cytotoxic chemotherapy. However, with rare exceptions, metastatic cancers were considered to be incurable by traditional therapy. Over the past 20 years a fourth modality - immunotherapy - has emerged as a potentially curative approach for patients with advanced metastatic cancer.

Tumor mechanisms of resistance to immune attack.

The immune system plays a key role in the interactions between host and tumor. Immune selection pressure is a driving force behind the sculpting and evolution of malignant cancer cells to escape this immune attack. Several common tumor cell-based mechanisms of resistance to immune attack have been identified and can be broadly categorized into three main classes: loss of antigenicity, loss of immunogenicity, and creation of an immunosuppressive microenvironment.

Targeting Multiple Receptors to Increase Checkpoint Blockade Efficacy.

Immune checkpoint blockade therapy is a powerful treatment strategy for many cancer types. Many patients will have limited responses to monotherapy targeted to a single immune checkpoint. Both inhibitory and stimulatory immune checkpoints continue to be discovered.

A Mechanism of Resistance to Antibody-Targeted Immune Attack.

Targeted monoclonal antibody therapy is a promising therapeutic strategy for cancer, and antibody-dependent cell-mediated cytotoxicity (ADCC) represents a crucial mechanism underlying these approaches. The majority of patients have limited responses to monoclonal antibody therapy due to the development of resistance. Models of ADCC provide a system for uncovering immune-resistance mechanisms.

Enhancing antibody-dependent cell-mediated cytotoxicity: a strategy for improving antibody-based immunotherapy.

The targeting of surface antigens expressed on tumor cells by monoclonal antibodies (mAbs) has revolutionized cancer therapeutics. One mechanism of action of antibody-based immunotherapy is the activation of immune effector cells to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). This review will summarize the process of ADCC, its important role in the efficacy of mAb therapy, how to measure it, and finally future strategies for antibody design that can take advantage of it to improve clinical performance.

Glomerular hyperfiltration in children with cancer: prevalence and a hypothesis.

Background: Glomerular hyperfiltration has recently been reported in children with malignancies and has been attributed to increased solute from breakdown of tumor tissues.

Objective: To evaluate the prevalence of hyperfiltration in the pediatric oncology population and explore its pathophysiological mechanism.

Materials And Methods: Tc-99 m diethylenetriaminepentaacetic acid (DTPA) glomerular filtration rate (GFR) examinations (437 studies) and medical records of 177 patients <21 years of age diagnosed with a malignancy between January 2005 and October 2013 were retrospectively reviewed.

For staining of ALK protein, the novel D5F3 antibody demonstrates superior overall performance in terms of intensity and extent of staining in comparison to the currently used ALK1 antibody.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm. Approximately 50 % of IMTs show an anaplastic lymphoma kinase (ALK) gene fusion resulting in ALK overexpression on immunohistochemistry (IHC). A novel anti-ALK monoclonal antibody (D5F3) has been suggested to be of superior sensitivity to the ALK1 antibody which is currently used.

The utility of STAT6 and ALDH1 expression in the differential diagnosis of solitary fibrous tumor versus prostate-specific stromal neoplasms.

Solitary fibrous tumor (SFT) diagnosis in prostate can be challenging on small biopsies. Prostatic stromal tumors of unknown malignant potential (STUMP) and SFT have overlapping features. NAB2-STAT6 gene fusions that were recently identified in various SFTs lead to nuclear translocalization of STAT6.

Endothelial monocyte activating polypeptide-II modulates endothelial cell responses by degrading hypoxia-inducible factor-1alpha through interaction with PSMA7, a component of the proteasome.

The majority of human tumors are angiogenesis dependent. Understanding the specific mechanisms that contribute to angiogenesis may offer the best approach to develop therapies to inhibit angiogenesis in cancer. Endothelial monocyte activating polypeptide-II (EMAP-II) is an anti-angiogenic cytokine with potent effects on endothelial cells (ECs).