Antibody-Cytokine Fusion Proteins for the Therapy of Breast Cancer

Antibody-Cytokine Fusion Proteins for the Therapy of Breast Cancer
Author:
Publisher:
Total Pages: 133
Release: 2002
Genre:
ISBN:

In this grant we proposed to explore the use of genetically engineered antibodies as therapeutic agents specifically attempting to augment and potentiate the host immune defense systems against breast cancer. The antibodies were to be specific for HER2/neu, a molecule present on the surface of many breast cancers; its increased expression is associated with poor prognosis. To these antibodies we proposed to join the cytokines IL-2, IL-12, and GM-CSF. Expression of these cytokines by cancer cells has been shown to render them immunogenic. The anti- HER2/neu antibody fusion proteins were intended to localize the cytokine at the tumor where it is expected to elicit an immune response. To accomplish our goals we proposed three specific aims. Specific Aim 1: To produce rL-2, IL-12, GM-CSF antibody fusion proteins specific for HER2/neu. Specific Aim 2: To evaluate the properties of the antibody fusion proteins in vitro. Specific Aim 3: To determine the properties of the antibody fusion proteins in vivo and their effectiveness in causing anti-tumor response. These there specific aims have been accomplished by the end of the third year of the present award.

Specificity, Function, and Development of NK Cells

Specificity, Function, and Development of NK Cells
Author: Klas Kärre
Publisher: Springer Science & Business Media
Total Pages: 250
Release: 2012-12-06
Genre: Medical
ISBN: 3642468594

Our understanding of the function of natural killer (NK) cells has dramatically changed in recent years. The discovery of NK receptors specific for MHC class I molecules, and the study of the role of co-stimulatory and adhesion molecules have led to an understanding of how NK cells recognize tumor and virally infected cells that have lost expression of MHC class I molecules or have altered distribution of normal cell surface molecules. Such recognition events lead to intracellular signals which can be either stimulatory or inhibitory. This book provides an insight into how NK cells develop, how they learn to distinguish altered cells from normal cells, and into their biological role in controlling infections and tumors.

Safety of Biologics Therapy

Safety of Biologics Therapy
Author: Brian A. Baldo
Publisher: Springer
Total Pages: 623
Release: 2016-08-12
Genre: Medical
ISBN: 3319304720

This long overdue title provides a comprehensive, up-to-date, state-of-the art review of approved biologic therapies, with coverage of mechanisms of action, Indications for therapy, immunogenicity and a detailed examination of adverse effects and safety of the many and diverse therapeutic agents presented in a total of 13 chapters. It is predicted that by 2016, biologics will make up half of the world's 20 top-selling drugs and by 2018, biologic medicine sales will account for almost half of the world's 100 biggest selling drugs. Recombinant proteins dominate the growing list of the more than 200 approved biotherapeutic agents with targeted antibodies, fusion proteins and receptors; cytokines; hormones; enzymes; proteins involved in blood-clotting, homeostasis and thrombosis; vaccines; botulinum neurotoxins; and, more recently, biosimilar preparations, comprising the majority of approved biologics. Written with clinicians, other health care professionals, and researchers in mind, Safety of Biologics Therapy examines, in a single volume, the full range of issues surrounding the safety of approved biologic therapies. A good understanding of the risks and safety issues of modern biologics therapy is increasingly being demanded of all those connected with their development, handling, prescribing, administration and subsequent patient management. In addition to being of great value to clinicians in all branches of medicine, and to nurses, pharmacists and researchers, this book will prove invaluable for students taking undergraduate and graduate courses in the above disciplines and in the biomedical sciences.

Antibody-IL2 Fusion Protein Delivery by Gene Transfer

Antibody-IL2 Fusion Protein Delivery by Gene Transfer
Author:
Publisher:
Total Pages: 0
Release: 1999
Genre:
ISBN:

Over the past year our team has been actively investigating the immunotherapeutic potential of the antibody-cytokine fusion proteins. These molecules contain the antibody portion recognizing the tumor associated antigens, and is covalently linked to a potent immune stimulator. HuKS-1L2 fusion protein which is highly reactive with breast cancer cells became available to us for in vitro and in animal in vivo studies. We are still actively pursuing experiments to elucidate the mechanisms of targeting tumor cells for destruction and mechanisms of stimulation immune effector cells by this molecule, to ultimately translate these findings to clinical application. At this time similar fusion protein (hul4.l8-1L2) became available for clinical testing and we decided to refocus our efforts in this direction. At the UW-CCC we are currently performing an initial Phase I clinical trial involving an administration of this novel immunocytokine to the patients with GD-2 positive tumors, delivered as a single agent therapy. We are collecting serum specimens as well as cells from these patients. Studies are underway to assess the effects of this treatment, its safety and future applications. Findings from these studies will provide a baseline for clinical testing of other immunocytokines targeting human cancers.