Boston, MA, United States

Dana-Farber Cancer Institute

www.dana-farber.org
Boston, MA, United States

Dana–Farber Cancer Institute is a center for cancer treatment and research in Boston, Massachusetts. It is a major affiliate of Harvard Medical School, and a founding member of Dana–Farber/Harvard Cancer Center, a Comprehensive Cancer Center designated by the National Cancer Institute. Wikipedia.


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Patent
Brigham, Women's Hospital, Dana-Farber Cancer Institute and National University of Singapore | Date: 2017-02-01

Described herein are methods and compositions which lead to the efficient ex vivo expansion of hematopoietic cells, such as hematopoietic stem cells (HSCs) and hematopoietic stem and progenitor cells HSPCs. Using combinations of small molecule drugs and cytokines/growth factors/grown factors targeting epigenetic status in cells, significant improvements in the expansion of cells was observed, including cells isolated from human cord blood or peripheral mobilized stem/progenitor cells. Multiple genes implicated in HSPC function were unperturbed, and efficiency of genomic editing using lentivirus was greatly enhanced following treatment. These novel approaches could be used therapeutically in a variety of hematopoietic transplantation settings, in addition to benefiting gene therapy techniques.


Patent
Harvard University and Dana-Farber Cancer Institute | Date: 2017-03-15

Aspects of the disclosure provide fusion proteins that bind cells expressing one or more target molecules including, for example, one or more cell surface multisubunit signaling receptors (e.g., EGFRvIII-expressing cells that also express interferon receptors) and that induce anti-proliferative effects, and related compositions and methods for the treatment of cancer.


The present invention is based on the identification of novel biomarkers predictive of responsiveness to anti-immune checkpoint inhibitor therapies.


Patent
Dana-Farber Cancer Institute | Date: 2017-03-22

In one aspect, a method for forming particles is provided. The method may allow biocompatible particles comprising an agent (e.g., pharmaceutically active agent) to be produced absent one or more purification step (e.g., removal of excess reagent). In certain embodiments, particles, produced as described herein, can be utilized in a pharmaceutical composition and/or administered to a subject without further purification. The lack of one or more purification step may simplify manufacturing and/or minimize or eliminate the loss of agent from the particle after formation. In some embodiments, the method comprises associating albumin with an agent and crosslinking to form particles, such that little or no cytotoxic molecules are produced and/or remain after particle formation. Cross-linked albumin particles formed via the methods described herein may serve as biocompatible carriers for a variety of agents.


The present invention is based on the identification of novel biomarkers predictive of responsiveness to anti-immune checkpoint inhibitor therapies.


Patent
Dana-Farber Cancer Institute | Date: 2017-06-14

The present disclosure provides compounds of Formula (I), and pharmaceutically compositions thereof. Compounds of Formula (I) have been found to bind bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits of the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, neurological diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.


Patent
Dana-Farber Cancer Institute | Date: 2017-06-14

The present disclosure provides compounds of Formula (I), and pharmaceutically compositions thereof. Compounds of Formula (I) have been found to bind bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits of the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, neurological diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.


PGC1α is a key transcriptional coregulator of oxidative metabolism and thermogenesis. Through a high-throughput chemical screen, we found that molecules antagonizing the TRPVs (transient receptor potential vanilloid), a family of ion channels, induced PGC1α expression in adipocytes. In particular, TRPV4 negatively regulated the expression of PGC1α, UCP1, and cellular respiration. Additionally, it potently controlled the expression of multiple proinflammatory genes involved in the development of insulin resistance. Mice with a null mutation for TRPV4 or wild-type mice treated with a TRPV4 antagonist showed elevated thermogenesis in adipose tissues and were protected from diet-induced obesity, adipose inflammation, and insulin resistance. This role of TRPV4 as a cell-autonomous mediator for both the thermogenic and proinflammatory programs in adipocytes could offer a target for treating obesity and related metabolic diseases. Copyright © 2012 Elsevier Inc. All rights reserved.


Kimmelman A.C.,Dana-Farber Cancer Institute
Genes and Development | Year: 2011

Macroautophagy (referred to hereafter as autophagy) is a highly regulated cellular process that serves to remove damaged proteins and organelles from the cell. Autophagy contributes to an array of normal and pathological processes, and has recently emerged as a key regulator of multiple aspects of cancer biology. The role of autophagy in cancer is complex and is likely dependent on tumor type, stage, and genetic context. This complexity is illustrated by the identification of settings where autophagy acts potently to either promote or inhibit tumorigenesis. In this review, I discuss the underlying basis for these opposing functions and propose a model suggesting a dynamic role for autophagy in malignancy. Collectively, the data point to autophagy as serving as a barrier to limit tumor initiation. Once neoplastic lesions are established, it appears that adaptive changes occur that now result in positive roles for autophagy in malignant progression and in subsequent tumor maintenance. Remarkably, constitutive activation of autophagy is critical for continued growth of some tumors, serving to both reduce oxidative stress and provide key intermediates to sustain cell metabolism. Autophagy is also induced in response to cancer therapies where it can function as a survival mechanism that limits drug efficacy. These findings have inspired significant interest in applying anti-autophagy therapies as an entirely new approach to cancer treatment. It is now apparent that aberrant control of autophagy is among the key hallmarks of cancer. While much needs to be learned about the regulation and context-dependent biological functions of autophagy, it seems clear that modulation of this process will be an attractive avenue for future cancer therapeutic approaches. © 2011 by Cold Spring Harbor Laboratory Press.


Hemler M.E.,Dana-Farber Cancer Institute
Nature Reviews Cancer | Year: 2014

An abundance of evidence shows supporting roles for tetraspanin proteins in human cancer. Many studies show that the expression of tetraspanins correlates with tumour stage, tumour type and patient outcome. In addition, perturbations of tetraspanins in tumour cell lines can considerably affect cell growth, morphology, invasion, tumour engraftment and metastasis. This Review emphasizes new studies that have used de novo mouse cancer models to show that select tetraspanin proteins have key roles in tumour initiation, promotion and metastasis. This Review also emphasizes how tetraspanin proteins can sometimes participate in tumour angiogenesis. These recent data build an increasingly strong case for tetraspanins as therapeutic targets.

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