GM-CSF and IL-4 Therapy for In-situ Expansion of Dendritic Cells and Enhancement of Vaccine-Based Immunity
Dendritic cells (DC) are a group of professional antigen presenting cells (APC) that provide a central stimulus for the generation of cell-mediated responses against foreign antigens. Dendritic cells are ubiquitously distributed throughout the body, where they pick up antigens, process them, and migrate to T-cell enriched areas of lymphoid tissue to activate corresponding antigen-specific T-cell clones.1 A major limitation in the human response to foreign challenges, including infections and tumors, is the limited number of DC and their suppression in individuals suffering from these conditions. As a result, patients often fail to respond to vaccines that might otherwise be effective.Previous in vitro data indicated that granulocyte-macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), when used in combination, induce precursor cells, such as CD34+ stem cells and monocytes, to mature into dendritic cells. These cells were classified as DC by their expression of cell surface markers characteristic of DC cells (CD83, CD40, CD86, CD11c, etc.), by their ability to take-up and process antigens, and by their ability to stimulate the proliferation of T cells in an antigen-specific manner. The strategy of using GM-CSF AND IL-4 to enhance the number and/or function of antigen presenting cells (including dendritic cells) in the blood, tissues and lymphoid organs of patients may be employed as a mechanism to improve the immune responses of individuals with a suppressed immunity. Therefore, this method has implications in treating conditions such as cancer, infections, AIDS, malnutrition and shock. Cytokine therapy using GM-CSF and IL-4 may further be implemented into immunization and vaccination strategies for infections that respond poorly to conventional vaccine approaches. Examples of these indications include AIDS, pneumonia, and tuberculosis.This cytokine combination therapy produced promising tumor responses in Phase I testing and is currently being tested in Phase II studies in patients with prostate cancer. Additional preclinical testing is ongoing to optimize combination therapy with vaccines, to better evaluate the form and function of the dendritic cells generated, and to evaluate the use of combination cytokine therapy as a mechanism for harvesting DC for use in the production of cell-based vaccines.
Patent Number: US6838081B1
Application Number: US2000647248A
Inventor: Roth, Michael Derek | Figlin, Robert Alan | Kiertscher, Sylvia Marie | Gitlitz, Barbara Jennifer
Priority Date: 2 Apr 1998
Priority Number: US6838081B1
Application Date: 17 Nov 2000
Publication Date: 4 Jan 2005
IPC Current: A61K003819 | A61K003820 | A61K003900 | C12N000508
US Class: 4240937 | 4240852 | 4240857 | 42409371 | 435355 | 435366 | 435372 | 435374 | 435377 | 435384 | 435386 | 435423
Assignee Applicant: The Regents of the University of California
Title: Methods for enhancing antigen-presenting cells and anti-tumor responses in a human patient
Usefulness: Methods for enhancing antigen-presenting cells and anti-tumor responses in a human patient
Summary: The new method is used to increases an antitumor immune response in humans (claimed). The tumor treated with the methods is selected from pancarcinoma, breast, small cell lung, non-small cell lung, gastrointestinal, prostate, bladder, ovarian, melanoma, central nervous system tumors, leukemias, lymphomas and sarcomas (claimed). The method may also be used to enhance the in vivo development of a population of CD14+ or CD83+ antigen presenting precursor cells within peripheral blood in a human (claimed).
Novelty: Reducing tumor size in patients
诊断/治疗
癌症/肿瘤
6838081
Related Materials Granulocyte Macrophage Colony-stimulating Factor and Interleukin 4 Enhance the number and Antigen-presenting Activity of Circulating CD14+ and CD83+ Cells in Cancer Patients. Cancer Research. (2000) Tech ID/UC Case 20088/1998-556-0 Related Cases 1998-556-0
Increased Dendritic Cell Number and Function Following Continuous in vivo Infusion of GM-CSF and IL-4. Blood. (2002)
Lentiviral Vector-mediated Autonomous Differentiation of Mouse Bone Marrow Cells into Immunologically Potent Dendritic Cell Vaccines. Molecular Therapy. (2007)
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