WO1996013275A9 - Procedes et produits permettant d'ameliorer les reactions immunitaires - Google Patents
Procedes et produits permettant d'ameliorer les reactions immunitairesInfo
- Publication number
- WO1996013275A9 WO1996013275A9 PCT/US1995/013895 US9513895W WO9613275A9 WO 1996013275 A9 WO1996013275 A9 WO 1996013275A9 US 9513895 W US9513895 W US 9513895W WO 9613275 A9 WO9613275 A9 WO 9613275A9
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cell
- cytokine
- cells
- antigen
- antigen presenting
- Prior art date
Links
Definitions
- the present invention features a method for enhancing an immune response by exposing an immune cell to an antigen presenting cell having adsorbed cytokine.
- xenogeneic is meant from a member of a different species.
- B cell is meant a cell that has the potential to produce immunoglobulin.
- tumor cell is meant cell the exhibits unregulated growth.
- autologous tumor cell is meant a tumor cell derived from the same tumor that is in a patient.
- dendritic cell is meant an antigen presenting cell with multiple cytoplasmic extensions circulating in the peripheral blood and expressing Class II MHC molecules.
- Self-association occurs when two or more molecules of the same type interact with each other so as to noncovalently bind together.
- the same type is meant that the molecules have the same function.
- self- associated IL-2 refers to multiple molecules of IL-2 interacting with each other
- non-IL-2 self-associated cytokines refers to other cytokines that interact with each other.
- Intercalation into the lipid bilayer is anchoring in the lipid bilayer of the plasma membrane that is based on non-specific hydrophobic interacts and does not involve specific binding to proteins.
- the invention features an artificial antigen presenting cell having adsorbed cytokine.
- artificial antigen presenting cell is meant an antigen presenting cell that does not have cytokine naturally bound to its surface or the cytokine is bound in different manner than occurs in nature or the cytokine is bound at greater amounts than naturally occurs on that cell.
- the cell has been manipulated in vitro to load the cytokine onto the cell surface.
- cytokine cytokine
- cytokines such as IL-2
- IL-2 do not naturally circulate systemically, but are produced physiologically for local consumption.
- the therapeutic potential of intravenous IL-2 therapy has been considerably restricted by the extraordinary toxicity that is associated with its systemic inoculation (S. Rosenberg et al., N. Engl . J. Med. , 316:889 (1987) ; W. Urba et al., Cancer Res . , 50:185 (1990) ; and K. Margolin et al . , J " . Clin . Oncol . , 7:484 (1989)) .
- cytokine IL-2
- IL-2 adsorbed to an antigen presenting cell induces a more powerful proliferative response than the same antigen presenting cell without adsorbed IL-2.
- "he delivery of IL-2 to a cell surface is predicated upon the discovery of the capability of cell surfaces to load IL-2, taking into account the propensity of the IL-2 molecule to self- associate upon binding to the surface. Self-association allows for large amounts of IL-2 to be localized to the cell surface where the antigen is also present .
- the amount of IL-2 adsorbed is estimated to be approximately 50-100,000 molecules per cell. The amount can be varied by incubating the cell with various concen ⁇ trations of IL-2. As few as 100 cells with adsorbed IL-2 can initiate significant proliferation in IL-2 receptor positive cells when co-cultured. IL-2 adsorbed to cells that do not possess the chain of the receptor complex cannot be removed by acid treatment with pH 2.5 medium. IL-2 adsorbed to cells through the chain can be removed by treatment with acid, pH 4.0.
- This invention encompasses the adsorption of cytokine to an antigen presenting cell and administration of the antigen presenting cell with cytokine adsorbed to a patient. Selection of the antigen presenting cell and the particular cytokine to be absorbed, is based on the disease to be treated. For example treatment of a particular type of cancer entails isolation of tumor cells of the cancer, irradiation of these cells to prevent growth, and adsorption with IL-2. Inoculation of these IL-2 adsorbed tumor cells back into the patient acts to induce or enhance an immune response to the tumor and results in tumor regression. Immunodeficient patients, such as those infected with Human Immunodeficiency Virus (HIV), do not respond well to vaccines.
- HIV Human Immunodeficiency Virus
- IL-2 Binding of IL-2 was accomplished using 2000 nM in 10% fetal bovine serum in phosphate buffered saline as previously described in Example 1. Cells were assayed for IL-2 binding as in Example 1. This experiment indicates that IL-2 is bound to both freshly isolated dendritic cells (Fig. 5A) and cultured dendritic cells (Fig. 5B) .
- Other embodiments are within the following claims.
Abstract
La présente invention concerne un procédé permettant d'améliorer une réaction immunitaire. Il comprend l'étape consistant à exposer une cellule immune à une cellule présentant un antigène et sur laquelle de la cytokine est adsorbée.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33241894A | 1994-10-31 | 1994-10-31 | |
| US08/332,418 | 1994-10-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1996013275A1 WO1996013275A1 (fr) | 1996-05-09 |
| WO1996013275A9 true WO1996013275A9 (fr) | 1996-08-22 |
Family
ID=23298146
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1995/013895 WO1996013275A1 (fr) | 1994-10-31 | 1995-10-27 | Procedes et produits permettant d'ameliorer les reactions immunitaires |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1996013275A1 (fr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5830464A (en) * | 1997-02-07 | 1998-11-03 | Fordham University | Compositions and methods for the treatment and growth inhibition of cancer using heat shock/stress protein-peptide complexes in combination with adoptive immunotherapy |
| US20150010630A1 (en) * | 2011-12-29 | 2015-01-08 | Trustees Of Tufts College | Functionalization of biomaterials to control regeneration and inflammation responses |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE129746T1 (de) * | 1990-09-14 | 1995-11-15 | Univ Johns Hopkins | Verfahren und zusammensetzungen für gentherapie und stärkung des immunsystems. |
| DE69230506T2 (de) * | 1991-10-25 | 2000-06-21 | Sidney Kimmel Cancer Center, San Diego | Lymphokine gentherapie bei krebs in kombination mit tumorantigenen |
| US5270038A (en) * | 1992-01-23 | 1993-12-14 | Board Of Regents, The University Of Texas System | Tumor necrosis factor receptors on microorganisms |
| IT1261180B (it) * | 1993-02-10 | 1996-05-09 | Metodo di propagazione in vitro di cellule til. |
-
1995
- 1995-10-27 WO PCT/US1995/013895 patent/WO1996013275A1/fr active Application Filing
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