The University of Texas System

Introgen Therapeutics Inc.

Elizabeth A Grimm

Jack A Roth

Wei-Wei Zhang

Tapas Mukhopadhyay

Toshiyoshi Fujiwara

Laurie B Owen-Schaub

Abner Mhashilkar

Rajagopal Ramesh

Keith Heaton

Raymond E Meyn

John B Mumm

The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

Methods and compositions comprising DNA damaging agents and p53

Methods and compositions comprising DNA damaging agents and P53

The properties of two recombinant human IL-2 analogues with mutations at Arginine 38 (.fwdarw.Alanine) and Phenylalanine 42 (.fwdarw.Lysine) were analyzed and compared to those of native IL-2. These analogues were found to maintain their ability to bind to the intermediate IL-2 receptor, p75, while binding only minimally to the high affinity p55+p75 receptor complex. The analogues also maintained the ability to stimulate peripheral blood mononuclear cells to generate lymphokine activated killing (LAK). However, IL-1.beta. and TNF-.alpha. secretion were significantly reduced in response to the analogues, as compared to the native IL-2 molecule. These analogues are therefore potentially valuable low-toxicity alternatives to IL-2 in human immunotherapy and adoptive immunotherapy treatment strategies.

Low toxicity interleukin-2 analogues for use in immunotherapy

Growing community of inventors

Houston, TX, United States of America

Elizabeth A Grimm