The General Hospital Corporation

Other

The Brigham and Women's Hospital, Inc.

Dana-farber-cancer Institute Inc.

Boston University

E Antonio Chiocca

Xandra O Breakefield

John D Wright

Yoshinaga Saeki

Richard Y Chung

Thomas S Deisboeck

Ling Chen

Mark Suter

Elliott D Kieff

Gosse Jan Adema

Fengfeng Bei

Mathias Ackermann

David J Waxman

Cornel Fraefel

Fred Hochberg

Fred Wang

Richard Wade-Martins

Xiaoqun Jiang

Ming X Wei

Ken Shortman

Kurt Tobler

The present application relates to sequences that enhance permeation of immunotherapy agents across the blood brain barrier (BBB), compositions comprising the sequences, and methods of use thereof to treat brain cancer, e.g., glioblastoma (GBM). Further disclosed are a number of potential targeting peptide sequences identified that enhance permeation through the BBB, when inserted into the capsid of an adeno-associated virus (AAV).

Methods and compositions for delivery of immunotherapy agents across the blood-brain barrier to treat brain cancer

The present invention relates to herpes viral mutants and methods of using these viral mutants for selectively targeting tumor cells or other populations of target cells. The viral mutants of the invention are capable of selective targeting due to the use of tumor-specific and/or cell-specific promoters to drive expression of the herpes &#x3b3;34.5 gene.

Cell-specific and/or tumor-specific promoter retargeting of herpes &#x3b3; 34.5 gene expression

The present invention relates to HSV-based amplicon vectors carrying a genomic DNA fragment, and methods of constructing and using the same. Included within the present invention is a method of converting any large capacity DNA cloning vector, such as a BAC or PAC, into an HSV amplicon or hybrid HSV amplicon using site-specific, or other types of recombination, so that genomic DNA inserts within the BAC or PAC clone can be delivered by infection to a cell, and efficiently expressed. The present invention also relates to a system for the rapid creation of viral vectors carrying transgenes of interest. This aspect of the invention is accomplished through recombination between: (a) a large-capacity cloning vector carrying a viral genome, and (b) a transfer vector containing the transgene of interest. Finally, an expression-ready genomic DNA library is disclosed.

Viral delivery system for infectious transfer of large genomic DNA inserts

The invention relates to devices and methods for growing cells in vitro in an enclosed device that allows for a three-dimensional measurement over time of both their proliferative and/or invasive properties. By growing the cells in an enclosed matrix that resembles the environment that the cells confront in vivo, the cells can divide, invade, and form branched networks as they do in living tissue, e.g., in an individual. The devices of the invention include a test chamber in which cells, e.g., tumor cells, are placed and permitted to divide and/or invade. Cells can be placed within an insert within a chamber of the device. A delivery chamber that connects to the test chamber enables the delivery of agents that can be studied, e.g., for their therapeutic potential. The assay devices of the invention can be used as model systems to study cancer biology and to evaluate the efficacy of anti-cancer therapeutics.

Three-dimensional cell growth assay

The present invention relates to viral mutants and methods of using these viral mutants for selectively killing neoplastic cells. The viral mutants of the invention are capable of selectively killing neoplastic cells by a combination of viral mediated oncolysis and anti-cancer (&ldquo;suicide&rdquo;) gene therapy.

Combination viral-based and gene-based therapy of tumors

The present invention relates to an enhanced and simplified herpes virus amplicon packaging system. The packaging system comprises a herpes virus amplicon vector and a packaging vector. In one embodiment, the packaging vector comprises a bacterial artificial chromosome (BAC) containing the HSV-1 genome. The packaging vector contains an intact pac site but is otherwise rendered packaging defective. The packaging vector can be rendered packaging defective by inserting nucleotides into the pac site, or by otherwise interfering with the capsid's ability to close, for example, by increasing the size of the DNA fragment upon which the herpes virus genome is cloned. This system can be used to package a wide range of nucleotide sequences (e.g., a therapeutic or antigenic gene) into an empty herpes virus particle taking advantage of the large transgene capacity of herpes viruses. This system can also be used as a vaccine to induce protective immunity against HSV-1, or other complex pathogens.

Enhanced packaging of herpes virus amplicons and generation of recombinant virus vectors

The present invention relates to a viral vector system derived from Epstein-Barr Virus (EBV), where the transgene is effectively inserted into the EBV major internal repeat region (IR1) without adverse affect on EBV latent or lytic function. The vector of the invention can target and stably transform B-lymphocyte cells, both in culture and in vivo.

Non-defective Epstein-Barr viral vector

A method for selectively killing nervous system and peripheral neoplastic cells is provided. Viral vectors are used to selectively express a cytochrome P450 gene in neoplastic cells, whose gene product targets the cells for selective killing, by rendering the cells sensitive to a chemotherapeutic agent.

Method of selectively destroying neoplastic cells

Growing community of inventors

Wakefield, MA, United States of America

E Antonio Chiocca