Massachusetts Institute of Technology

Whitehead Institute for Biomedical Research

The Broad Institute, Inc.

Aveo Pharmaceuticals, Inc.

Tyler E Jacks

Daniel Griffith Anderson

Joseph R Dorkin

Hao Yin

Wen Xue

David A Canner

Hidde L Ploegh

Omar Khan

Jasdave S Chahal

Robert Samuel Langer

Aviv Regev

Paul Blainey

Steven C Clark

Murray Robinson

Ronan O'Hagan

Robert S Langer

Rebecca H Herbst

Yinghui Zhou

Ronald A Depinho

Joerg Heyer

William Rideout, Iii

Leah Marie Schmidt

Joseph L Kissil

Amy Li

David Feldser

Georgia Lagoudas

Ronald Depinho

Chengcheng Jin

William Iii Rideout

Compositions and methods for modified dendrimer nanoparticle ('MDNP') delivery of therapeutic, prophylactic and/or diagnostic agent such as large repRNA molecules to the cells of a subject have been developed. MDNPs efficiently drive proliferation of antigen-specific T cells against intracellular antigen, and potentiate antigen-specific antibody responses. MDNPs can be multiplexed to deliver two or more different repRNAs to modify expression kinetics of encoded antigens and to simultaneous deliver repRNAs and mRNAs including the same UTR elements that promote expression of encoded antigens.

Compositions and methods for modified dendrimer nanoparticle delivery

The present disclosure relates to compositions and methods for modifying a gene sequence, and for systems for delivering such compositions. For example, the disclosure relates to modifying a gene sequence using a CRISPR-Cas9 or other nucleic acid editing system, and methods and delivery systems for achieving such gene modification, such as viral or non-viral delivery systems.

Method for gene editing

The present invention discloses novel methods, compositions, and uses thereof for removing or overcoming immunosuppression. More specifically, the methods and compositions disclosed herein target effector Tcells by modulating ST2 and/or IL-33 signaling using pharmaceutical inhibitors and/or genetic ablation, whereby the levels and/or activities of effector Tcells in a tumor microenvironment are inhibited, and the infiltration of effector CD8cytotoxic T cells into tumor microenvironment increases. As a result, tumor growth is inhibited and tumor volume is reduced. The present invention also provides methods for identifying and isolating effector Tcells in a population of heterogeneous cells.

Methods and compositions for overcoming immunosuppression

It has been discovered that lung tumor growth is associated with a dysregulation of the local microbiota, including an increased total bacterial load and reduced bacterial diversity in the airway. In the lungs, commensal bacteria, which are otherwise non-pathogenic and colonize pulmonary tissue at a much lower density in healthy individuals, provoke chronic inflammation and exacerbation of lung cancer through tumor-infiltrating immune cells. Thus, targeting the lung microbiota and its responding immune pathways is useful in treating lung cancer. Disclosed are compositions and methods targeting the lung microbiota and its responding immune pathways in a subject by specific targeting of commensal bacteria in the subject. Typically, the methods involve administering an effective amount of one or more therapeutics such as an antibiotic that reduces the local bacterial load, blocks or depletes tumor-infiltrating immune cells, and/or locally inhibits one or more cytokines or chemokines.

Methods and compositions targeting lung microbiota and its responding immune pathways for lung cancer treatment

Delivery systems and kits for gene editing

The invention relates to methods and related products for treatment and determining modes of treatment for cancer or prognosis of cancer. Preferably the methods are related to the induction of CD80 in p53 responsive cancer cells.

Methods and products related to targeted cancer therapy

Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.

Chimeric cancer models

The present inventions features methods for treating or preventing cancer (e.g., cancer of the central nervous system) by administering a compound that inhibits PAK kinase activity and/or merlin phosphorylation to a mammal (e.g., a human). The invention also provides screening methods for identifying additional inhibitors of PAK kinase activity and/or merlin phosphorylation.

Methods of screening for compounds that decrease phosphorylation of merlin and may be useful in cancer treatment

Growing community of inventors

Newtown, MA, United States of America

Tyler E Jacks