Memorial Sloan Kettering Cancer Center

Sloan-kettering Institute for Cancer Research

University of Texas System

Other

The General Hospital Corporation

Ceramide Therapeutics

Michigan State University

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Fundação D. Anna De Sommer Champalimaud E Dr. Carlos Montez Champalimaud

Vascular Biogenics Ltd.

Richard N Kolesnick

Jimmy Andrew Rotolo

Renata Pasqualini

Wadih Arap

Zvi Fuks

Hongmei R Xing

Adriana Haimovitz-Friedman

Evis Sala

Edward Howard Schuchman

Yechezkel Barenholz

Michel Sadelain

Dror Harats

Steven M Larson

Jonathan Lee Tilly

Jan Grimm

Erez Koren

Jun Liu

Yuhua Zhang

Julia Busik

Carlo Greco

Branka Stancevic

Nira Varda-bloom

Renate Pasqualini

Tuula Penate-Medina

Oula Penate-Medina

Daniel L J Thorek

Hongmei R Memorial Sloan Kettering Cancer Xing

The present disclosure provides methods and systems for treating tumors with radiotherapy, wherein a first dose of radiation is administered to a first sub-volume of the tumor and a second dose of radiation is administered to a second sub-volume of the tumor.

Perfusion modulated tumor dose sculpting with single dose radiotherapy

We have discovered that administering anti-ceramide antibody treats and prevents an array of diseases mediated by cytolytic T lymphocyte (CTLs)-induced killing and by damage to endothelial microvasculture, including radiation-induced GI syndrome, Graft vs. Host diseases, inflammatory diseases and autoimmune diseases. We have also discovered new anti-ceramide monoclonal antibodies, that have therapeutic use preferably in humanized form to treat or prevent these diseases.

Methods for treating GI syndrome and graft versus host disease

Disclosed is a method for enhancing tumor response to chemotherapy, the method comprising administering a short-acting anti-angiogenic agent (AAA) capable of activating ASMase to a subject afflicted with a solid tumor, and thereby creating a time interval of increased susceptibility of said tumor to one or more chemotherapeutic agents, followed by administration of at least one chemotherapeutic agent within the interval. The interval can be defined in terms of a short-duration activation of ASMase signaling by the AAA. Disclosed are also methods for predicting the tumor response in a patient afflicted with a solid tumor to a chemotherapeutic agent, using as an indicator of the response ASMase level or activity (or ceramide level) in the patient following the administration of the chemotherapeutic agent to the patient, or dynamic IVIM based DW-MRI to measure perfusion alterations following administration of the chemotherapeutic agent.

Enhancement of tumor response to chemotherapy by activation of the asmase/ceramide pathway through timed administration of a short-acting anti-angiogenic agent

Monoclonal antibodies directed to ceramide that inhibit apoptosis are disclosed. Humanized and scFv versions of the antibodies are also disclosed. Methods for prevention or treatment of apoptosis in a subject by administration of the anti-ceramide antibodies are disclosed.

Anti-ceramide antibodies

The present disclosure provides methods of treating diabetic retinopathy and ocular inflammatory diseases with anti-ceramide antibodies and antibody fragments.

Methods for treating diabetic retinopathy using anti-ceramide monoclonal antibody 2A2

It has been discovered that administering therapeutically effective amounts of an antibiotic that kills Gram-negative bacteria, together with an anti-ceramide antibody or anti-ceramide mimetic, treats and prevents an array of diseases mediated by cytolytic T lymphocyte (CTL)-induced killing and/or by damage to endothelial microvasculature, including Radiation GI syndrome, GvHD disease, inflammatory diseases and autoimmune diseases.

Enhancement of tumor response to chemotherapy by activation of the ASMase/ceramide pathway through timed administration of a short-acting anti-angiogenic agent

Based on the observation that the application of small amounts of exogenous acid sphingomyelinase to generate endogenous ceramide, or provision of exogenous long-chain natural C16-ceramide resulted in rapid translocation of vacuolar daunorubicin into the nucleus in multi-drug resistant (MDR) cells, the present invention relates to a nano-liposomal preparation that includes C16-ceramide. Exposure of MDR cells to the C16:0 ceramide-based nanoliposomes provide a mechanism to reverse MDR in chemoresistant cells and tumors, by inducing rapid translocation of chemotherapeutic agent from cytoplasmic vesicles to the nucleus.

Ceramide reversal of multi-drug resistance

Anti-ceramide monoclonal antibody 2A2

The present invention relates to methods and compositions for the specific inhibition of kinase suppressor of Ras (KSR). In particular, the invention provides genetic approaches and nucleic acids for the specific inhibition of KSR, particularly of KSR expression. The invention relates to antisense oligonucleotides and the expression of nucleic acid which is substantially complementary to KSR RNA. Oligonucleotide and nucleic acid compositions are provided. The invention provides methods to inhibit KSR, including inhibition of KSR expression. Methods for blocking gf Ras mediated tumorigenesis, metastasis, and for cancer therapy are provided. Methods for conferring radiosensitivity to cells are also provided.

Kinase suppressor of Ras inactivation for therapy of Ras mediated tumorigenesis

The present invention relates to methods and compositions for the specific inhibition of kinase suppressor of Ras (KSR). In particular, the invention provides genetic approaches and nucleic acids for the specific inhibition of KSR, particularly of KSR expression. The invention relates to antisense oligonucleotides and the expression of nucleic acid which is substantially complementary to KSR RNA. Oligonucleotide and nucleic acid compositions are provided. The invention provides methods to inhibit KSR, including inhibition of KSR expression. Methods for blocking gfRas mediated tumorigenesis, metastasis, and for cancer therapy are provided. Methods for conferring radiosensitivity to cells are also provided.

Growing community of inventors

New York, NY, United States of America

Richard N Kolesnick