WO1996013275A9 - Procedes et produits permettant d'ameliorer les reactions immunitaires - Google Patents

Procedes et produits permettant d'ameliorer les reactions immunitaires

Info

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
Application number
PCT/US1995/013895
Other languages
English (en)
Other versions
WO1996013275A1 (fr
Filing date
Publication date
Application filed filed Critical
Publication of WO1996013275A1 publication Critical patent/WO1996013275A1/fr
Publication of WO1996013275A9 publication Critical patent/WO1996013275A9/fr

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.
PCT/US1995/013895 1994-10-31 1995-10-27 Procedes et produits permettant d'ameliorer les reactions immunitaires WO1996013275A1 (fr)

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)

* Cited by examiner, † Cited by third party
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
EP2797641B1 (fr) * 2011-12-29 2019-07-10 Trustees Of Tufts College Fonctionnalisation de biomatériaux pour commander la régénération et des réponses à une inflammation

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992005262A1 (fr) * 1990-09-14 1992-04-02 The John Hopkins University Procedes et compositions pour la therapie et la potentialisation genetiques de l'immunite antitumorale
DK0668781T3 (da) * 1991-10-25 2000-04-17 Sidney Kimmel Cancer Ct Lymfokingenterapi af cancer i kombination med tumorantigener
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.

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