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.

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.

Immunotherapy of Hepatocellular Carcinoma

Immunotherapy of Hepatocellular Carcinoma
Author: Tim F. Greten
Publisher: Springer
Total Pages: 0
Release: 2018-08-22
Genre: Medical
ISBN: 9783319879116

In this book we provide insights into liver – cancer and immunology. Experts in the field provide an overview over fundamental immunological questions in liver cancer and tumorimmunology, which form the base for immune based approaches in HCC, which gain increasing interest in the community due to first promising results obtained in early clinical trials. Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death in the United States. Treatment options are limited. Viral hepatitis is one of the major risk factors for HCC, which represents a typical “inflammation-induced” cancer. Immune-based treatment approaches have revolutionized oncology in recent years. Various treatment strategies have received FDA approval including dendritic cell vaccination, for prostate cancer as well as immune checkpoint inhibition targeting the CTLA4 or the PD1/PDL1 axis in melanoma, lung, and kidney cancer. Additionally, cell based therapies (adoptive T cell therapy, CAR T cells and TCR transduced T cells) have demonstrated significant efficacy in patients with B cell malignancies and melanoma. Immune checkpoint inhibitors in particular have generated enormous excitement across the entire field of oncology, providing a significant benefit to a minority of patients.

Cell Surface Proteases

Cell Surface Proteases
Author:
Publisher: Elsevier
Total Pages: 475
Release: 2003-05-03
Genre: Science
ISBN: 0080490883

Cell Surface Proteases provides a comprehensive overview of these important enzymes that catalyze the hydrolysis of a protein as it degrades to a simpler substance. In the 1990s, an explosion of new discoveries shed light on the role of cell surface proteases and extended it beyond degradation of extracellular matrix components to include its influence on growth factors, cell signaling, and other cellular events. This volume unites the scientific literature from across disciplines and teases out unified themes of interactions between cell surface proteases and interconnecting cell surface-related systems -- including integrins and other adhesion molecules. Scientists and students involved in developmental biology, cell biology and disease processes will find this an indispensable resource. * Provides an overview of the entire field of cell surface proteases in a single volume* Presents major issues and astonishing discoveries at the forefront of modern developmental biology and developmental medicine * A thematic volume in the longest-running forum for contemporary issues in developmental biology with over 30 years of coverage