Disease Treatments Using Multimeric TNFSF Ligands
The advantages of this new form of CD40L are: Versatile - treatment for cancer and infectious disease agents such as HIV and Mycobacterium tuberculosis; vaccines; expanding immune cells; and diagnostic tests of immune function; may have utility in neutralizing autoimmune response in diseases such as lupus or multiple sclerosis. Potent - affects macrophages and B cells in the same manner as membrane CD40L.
UCSD researchers have developed an invention useful for: augmenting immunity (both cellular and antibodies) against cancer and infectious diseasesExpanding immune cells (B cells, dendritic cells, macrophages and T cells) in vitro for reinfusion of them or their productsImmunological testing of immune function. In one embodiment, the invention is a soluble recombinant fusion protein containing multiple CD40 ligands ("CD40L"). This protein affects macrophages and B cells in the same manner as membrane CD40L. The same technology can be applied to produce other members of the TNF family, such as TNF-alpha, FasL, TRAIL, RANKL, 4-1BBL, and others.
Patent Number: US7300774B1
Application Number: US1999454223A
Inventor: Kornbluth, Richard S.
Priority Date: 9 Dec 1999
Priority Number: US7300774B1
Application Date: 9 Dec 1999
Publication Date: 27 Nov 2007
IPC Current: C12P002102 | C07K0014525 | C07K0014705 | A61K003900
US Class: 4350695 | 530351
Assignee Applicant: The Regents of the University of California
Title: Multimeric fusion proteins of the TNF superfamily ligands
Usefulness: Multimeric fusion proteins of the TNF superfamily ligands
Summary: (III) is useful for stimulating immune response in potentially immunocompetant cells (e.g., resting B cells) which involves contacting the cells with (III) such that they are induced to proliferate. (III) is also useful for increasing antigenicity of cells such as tumor cells or human immunodeficiency virus (HIV) positive cells (claimed). The multimeric nature of (II) enables them to engage multiple receptor on the responding cells, thus mimicking the effects of membrane forms of these ligands. (III) is also useful as a vaccine adjuvant since it stimulates B cells, macrophages and dendritic cells. Since the large size of the soluble (III) makes them less likely to diffuse into the circulation, they can be advantageously used as a vaccine adjuvant or tumor immunotherapy agent, injected locally to prevent them from diffusing away. Also, the TNFSF-collectin fusion proteins present new possibilities for the expression of highly active, multimeric, soluble TNFSF members. CD40L was a powerful stimulant for macrophages and dendritic cells. So, preparations of CD40L-surfactant protein D (SPD) were added to monocyte-derived macrophages and the production of MIP-1 was used as a measure of stimulation. Both human and murine CD40L-SPD were able to stimulate macrophages, whereas the T147N-CD40L-SPD mutant was inactive as expected.
Novelty: Producing tumor necrosis factor superfamily proteins as multimeric ligands fused onto collectin molecules e.g. pulmonary surfactant protein D, useful as vaccine adjuvants against infectious agents and tumors
诊断/治疗
人类免疫缺陷病毒
7300774
Additional Technologies by these Inventors Tech ID/UC Case 19475/1999-003-0 Related Cases 1999-003-0
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