Kalivir Immunotherapeutics, Inc.

Carnegie Mellon University

Kalivir Immunotherapeutcs, Inc.

Mingrui Zhang

Stephen Howard Thorne

Daniel J Byrd

Alan S Waggoner

Subhasish K Chakraborty

The disclosure relates to modified oncolytic viruses. The modified oncolytic viruses of the disclosure comprise modification in the viral genome encoding exogenous nucleic acids to enhance the oncolytic immunotherapy by remodeling the tumor microenvironment and with enhanced systemic delivery. The disclosure further relates to compositions comprising the modified oncolytic viruses, kits containing the same, and methods of using the oncolytic viruses.

Oncolytic immunotherapy by tumor micro-environment remodeling

This disclosure provides a modified oncolytic virus that can contain modifications in the viral genome and exogenous nucleic acids coding for proteins. The modified oncolytic virus can be utilized as a platform vector for systemic delivery.

Platform oncolytic vector for systemic delivery

Described herein are modified oncolytic viruses that can contain modifications in the viral genome and exogenous nucleic acids coding for proteins. The modified oncolytic virus can be utilized as a platform vector for systemic delivery. Further described herein are oncolytic viruses having an exogenous nucleic acid that codes for a protein or a functional variant thereof that enhances degradation of an extracellular matrix (ECM) associated with a tumor, wherein the protein is a membrane associated protein.

The present disclosure provides for recombinant oncolytic viruses with gene deletions or insertions which result in downregulation of Major Histocompatibility Complex class I and alternatively or additively upregulation of Major Histocompatibility Complex class II. Immunologic and pharmaceutical compositions comprising these recombinant viruses and methods of using these compositions are also presented.

Oncolytic viruses for modified MHC expression

Tissue slices and whole organisms offer substantial challenges to fluorescence imaging. Autofluorescence and absorption via intrinsic chromophores, such as flavins, melanin, and hemoglobins, confound and degrade output from all fluorescent tags. An 'optical window,' farther red than most autofluorescence sources and in a region of low hemoglobin and water absorbance, lies between 650 and 900 nm. This valley of relative optical clarity is an attractive target for fluorescence-based studies within tissues, intact organs, and living organisms. Novel fluorescent tags were developed herein, based upon a genetically targeted fluorogen activating protein and cognate fluorogenic dye that yields emission with a peak at 733 nm exclusively when complexed as a 'fluoromodule'. This tool improves substantially over previously described far-red/NIR fluorescent proteins in terms of brightness, wavelength, and flexibility by leveraging the flexibility of synthetic chemistry to produce novel chromophores.

Growing community of inventors

Pittsburgh, PA, United States of America

Mingrui Zhang