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Engineering Challenges for Brain Tumor Immunotherapy.
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Engineering Challenges for Brain Tumor Immunotherapy.

Adv Drug Deliv Rev. 2017 Jun 15;:

Authors: Lyon JG, Mokarram N, Saxena T, Carroll SL, Bellamkonda RV

Abstract
Malignant brain tumors represent one of the most devastating forms of cancer with abject survival rates that have not changed in the past 60years. This is partly because the brain is a critical organ, and poses unique anatomical, physiological, and immunological barriers. The unique interplay of these barriers also provides an opportunity for creative engineering solutions. Cancer immunotherapy, a means of harnessing the host immune system for anti-tumor efficacy, is becoming a standard approach for treating many cancers. However, its use in brain tumors is not widespread. This review discusses the current approaches, and hurdles to these approaches in treating brain tumors, with a focus on immunotherapies. We identify critical barriers to immunoengineering brain tumor therapies and discuss possible solutions to these challenges.

PMID: 28625831 [PubMed - as supplied by publisher]




Bioengineering strategies for inducing tolerance in autoimmune diabetes.
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Bioengineering strategies for inducing tolerance in autoimmune diabetes.

Adv Drug Deliv Rev. 2017 Jun 15;:

Authors: Baekkeskov S, Hubbell JA, Phelps EA

Abstract
Type 1 diabetes is an autoimmune disease marked by the destruction of insulin-producing beta cells in the pancreatic islets. Strategies to delay onset or prevent the autoimmune recognition of beta cell antigens or T cell-mediated killing of beta cells have mainly focused on systemic immunomodulation and antigen-specific immunotherapy. To bridge the fields of type 1 diabetes immunology and biomaterials engineering, this article will review recent trends in the etiology of type 1 diabetes immunopathology and will focus on the contributions of emerging bioengineered strategies in the fight against beta cell autoimmunity in type 1 diabetes.

PMID: 28625830 [PubMed - as supplied by publisher]




Combinatorial immunotherapy and nanoparticle mediated hyperthermia.
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Combinatorial immunotherapy and nanoparticle mediated hyperthermia.

Adv Drug Deliv Rev. 2017 Jun 15;:

Authors: Moy AJ, Tunnell JW

Abstract
Immune checkpoint therapy has become the first widely adopted immunotherapy for patients with late stage malignant melanoma, with potential for a wide range of cancers. While some patients can experience long term disease remission, this is limited only to a subset of patients and tumor types. The path forward to expand this therapy to more patients and tumor types is currently thought to be combinatorial treatments, the combination of immunotherapy with other treatments. In this review, the combinatorial approach of immune checkpoint therapy combined with nanoparticle-assisted localized hyperthermia is discussed, starting with an overview of the different nanoparticle hyperthermia approaches in development, an overview of the state of immune checkpoint therapy, recent reports of immune checkpoint therapy and nanoparticle-assisted hyperthermia in a combinatorial approach, and finally a discussion of future research topics and areas to be explored in this new combinatorial approach to cancer treatment.

PMID: 28625829 [PubMed - as supplied by publisher]




Precision Monitoring of Immunotherapies in Solid Organ and Hematopoietic Stem Cell Transplantation.
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Precision Monitoring of Immunotherapies in Solid Organ and Hematopoietic Stem Cell Transplantation.

Adv Drug Deliv Rev. 2017 Jun 15;:

Authors: Diloreto R, Khush K, De Vlaminck I

Abstract
Pharmacological immunotherapies are a key component of post-transplant therapy in solid-organ and hematopoietic stem cell transplantation. In current clinical practice, immunotherapies largely follow a one-size fits all approach, leaving a large portion of transplant recipients either over- or under-immunosuppressed, and consequently at risk of infections or immune-mediated complications. Our goal here is to review recent and rapid advances in precision and genomic medicine approaches to monitoring of post-transplant immunotherapies. We will discuss recent advances in precision measurements of pharmacological immunosuppression, measurements of the plasma and gut microbiome, strategies to monitor for allograft injury and post-transplant malignancies via circulating cell-free DNA, and comprehensive measurements of the B and T cell immune cell repertoire.

PMID: 28625828 [PubMed - as supplied by publisher]




Cells as Advanced Therapeutics: State-of-the-art, Challenges, and Opportunities in Large Scale Biomanufacturing of High-Quality Cells for Adoptive Immunotherapies.
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Cells as Advanced Therapeutics: State-of-the-art, Challenges, and Opportunities in Large Scale Biomanufacturing of High-Quality Cells for Adoptive Immunotherapies.

Adv Drug Deliv Rev. 2017 Jun 15;:

Authors: Dwarshuis NJ, Parratt K, Santiago-Miranda A, Roy K

Abstract
Therapeutic cells hold tremendous promise in treating currently incurable, chronic diseases since they perform multiple, integrated, complex functions in vivo compared to traditional small-molecule drugs or biologics. However, they also pose significant challenges as therapeutic products because (a) their complex mechanisms of actions are difficult to understand and (b) low-cost bioprocesses for large-scale, reproducible manufacturing of cells have yet to be developed. Immunotherapies using T cells and dendritic cells (DCs) have already shown great promise in treating several types of cancers, and human mesenchymal stromal cells (hMSCs) are now extensively being evaluated in clinical trials as immune-modulatory cells. Despite these exciting developments, the full potential of cell-based therapeutics cannot be realized unless new engineering technologies enable cost-effective, consistent manufacturing of high-quality therapeutic cells at large-scale. Here we review cell-based immunotherapy concepts focused on the state-of-the-art in manufacturing processes including cell sourcing, isolation, expansion, modification, quality control (QC), and culture media requirements. We also offer insights into how current technologies could be significantly improved and augmented by new technologies, and how disciplines must converge to meet the long-term needs for large-scale production of cell-based immunotherapies.

PMID: 28625827 [PubMed - as supplied by publisher]




Drug Discovery and Therapeutic Delivery for the Treatment of B and T cell Tumors.
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Drug Discovery and Therapeutic Delivery for the Treatment of B and T cell Tumors.

Adv Drug Deliv Rev. 2017 Jun 15;:

Authors: Stephenson R, Singh A

Abstract
Hematological malignancies manifest as lymphoma, leukemia, and myeloma, and remain a burden on society. From initial therapy to endless relapse-related treatment, societal burden is felt not only in the context of healthcare cost, but also in the compromised quality of life of patients. Long-term therapeutic strategies have become the standard in keeping hematological malignancies at bay as these cancers develop resistance to each round of therapy with time. As a result, there is a continual need for the development of new drugs to combat resistant disease in order to prolong patient life, if not to produce a cure. This review aims to summarize advances in targeting lymphoma, leukemia, and myeloma in both cutting-edge and well established platforms. Current standard of treatment will be reviewed for these malignancies and emphasis will be made on new therapy development in the areas of antibody engineering, epigenetic small molecule inhibiting drugs, vaccine development, and chimeric antigen receptor cell engineering. In addition, platforms for the delivery of these and other drugs will be reviewed including antibody-drug conjugates, micro- and nanoparticles, and multimodal hydrogels. Lastly, we propose that tissue engineered constructs for hematological malignancies are the missing link in targeted drug discovery alongside mouse and patient-derived xenograft models.

PMID: 28625826 [PubMed - as supplied by publisher]