WO2001016342A9 - Use of lentiviral vectors for antigen presentation in dendritic cells - Google Patents
Use of lentiviral vectors for antigen presentation in dendritic cellsInfo
- Publication number
- WO2001016342A9 WO2001016342A9 PCT/US2000/023162 US0023162W WO0116342A9 WO 2001016342 A9 WO2001016342 A9 WO 2001016342A9 US 0023162 W US0023162 W US 0023162W WO 0116342 A9 WO0116342 A9 WO 0116342A9
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- vector
- hiv
- antigen
- cell
- dendritic cell
- Prior art date
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- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16041—Use of virus, viral particle or viral elements as a vector
- C12N2740/16043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Definitions
- the present invention provides, in general, a dendritic cell (DC) based vaccine and a strategy to induce virus specific cytotoxic T lymphocyte (CTL) immunity.
- DC dendritic cell
- CTL cytotoxic T lymphocyte
- the invention provides a method of inducing an immune response in a subject by administering to the subject a therapeutically effective amount of a DC, or of a progenitor thereof, transduced with a replication defective pseudotyped lentiviral vector having a nucleic acid sequence encoding an antigen, such that the antigen is presented on the surface of the dendritic cell.
- the nonfunctional gene products of a particular viral vector of the invention can be nonfunctional for various reasons.
- one or more of the gene products may be nonfunctional due to deletion of all or part of the nucleic acid sequences encoding the gene products; one or more other gene products may be nonfunctional due to the incorporation of a STOP codon in the encoding nucleic acid sequences; and still another gene product may be nonfunctional due to a directed mutation in a regulatory element required for its expression.
- These and other methods known in the art are useful for rendering selected gene products nonfunctional in a viral vector of the invention, and one or more of the methods can be used in constructing a single viral vector of the invention.
- DCs can be dividing or nondividing DCs.
- Useful procedures for separating and purifying cells include magnetic separation methods using antibody coated magnetic beads; affinity chromatography; cytotoxic agents linked to a monoclonal antibody or used in conjunction with a monoclonal antibody, for example, and complement and cytotoxins; "panning" with antibodies attached to a solid matrix such as a plastic plate; or any other convenient method.
- Accurate and efficient separation of particular cell types such as immature DCs can be performed using, for example, fluorescence activated cell sorters (FACS), which can have a plurality of color channels, low angle, and obtuse light scattering detecting channels, and impedance channels, to facilitate detection and separation of the desired cell type.
- FACS fluorescence activated cell sorters
- the lentiviral vectors of the invention are recombinant lentiviruses, particularly recombinant immunodeficiency disease viruses, including human immunodeficiency virus (HIN), feline immunodeficiency virus (FIN), simian immunodeficiency virus (SIN), and the like.
- the recombinant lentiviral vectors are replication defective and, therefore, cannot assemble into infectious virions unless they are propagated in the presence of an appropriate helper nucleic acid sequence, for example, in a helper virus containing cell line, in which appropriate sequences enabling encapsidation are expressed.
- the encoded polypeptide can be an HIV-1 gag, pol, env, vpr, vif, nef, vpx, tat, rev or vpu gene product, or a corresponding gene product from a related primate immunodeficiency virus, or other retrovirus or lentivirus.
- the invention provides a method of inducing an immune response in a subject by transducing a DC, or a progenitor of a DC, with a pseudotyped lentiviral vector, in vitro, including ex vivo, or in vivo, including in situ, to produce a transduced DC, which can be contacted with a T cell to produce an activated T cell. Also provided is a method of activating a T cell by contacting the T cell with a DC transduced with such a pseudotyped lentiviral vector.
- the clinical administration of retroviruses has been accomplished by the direct injection of virus into tissue, and by the administration of the retroviral producer cells.
- Methods for delivering retrovirus and retroviral producer cells to a subject are well known, and include intradermal, intramuscular, intravenous, intraperitoneal, and subcutaneous delivery.
- the pseudotyped lentivirus comprising a nucleic acid sequence encoding an antigen can be prepared as a formulation containing a pharmacologically effective dose in pharmaceutically acceptable medium, for example normal saline or phosphate buffered saline.
- the pharmaceutical composition additionally can contain a bactericidal agent, stabilizers, buffers, adjuvants, or the like.
- the virus can be administered as a single agent, or in combination with one or more other agents, including a therapeutic or immunostimulatory agent.
- the amount of a viral vector or other composition as disclosed herein that is administered to a subject will vary depending, for example, on the nature of the disease, the frequency of administration, the manner of administration, and the clearance of the agent from the subject. For example, a dose may be administered to a subject weekly or biweekly, or may be fractionated into smaller doses and administered daily or semiweekly to maintain an effective dosage level. Regardless of such factors, however, the composition is administered at a dosage sufficient to induce an immune response in the subject, the particular parameters being determined by phase I and phase II clinical studies as is routine in the art.
- Divalent cations such as Ca ++ , Ba ++ and Sr ++ can interact with guluronate, and the cooperative binding of these cations within the guluronate blocks provides the primary intramolecular crosslinking responsible for formation of stable ion-paired alginate gels.
- Alginate encapsulation methods generally take advantage of the gelling of alginate in the presence of these divalent cation solutions. In particular, these methods involve the suspension of the material to be encapsulated, in a solution of monovalent cation alginate salt, e.g., sodium.
- the cells were exposed to 1.0 % (w/v) sodium azide and red fluorescent microspheres to distinguish nonspecif ⁇ cally bound beads from phagocytosed beads.
- cells were separated from unengulfed beads by density gradient centrifugation (Steinkamp et al., Science 115: 64-66, 1982) and analyzed by FACS.
- irradiated mature DC 2000 rad, cesium 137 source
- PBL peripheral blood leukocytes
- 3 H-thymidine (1 ⁇ Ci/well; DuPont NEN, Boston, MA) was added 18 hr before harvest, using an automated cell harvester (Skatron, SterlingNA). Incorporation of 3 H-thymidine into the cells was quantified using a ⁇ -counter (Beckman; Fullerton CA).
- the ability of the T cells to lyse A2.1-Jurkat pulsed with known A2.1 -restricted epitopes of gag andpol is tested (e.g., pol: p476-484; p652-660; gag, p77-85).
- the novel epitopes are identified by pulsing A2.1 -Jurkat cells with a panel of nanomeric peptides overlapping by three residues encoding known immunogenic regions of gag, pol or accessory proteins (e.g., rev, tat, vif).
- These stably transduced Mo-DC can be used for repeated immunization in vivo or for ex vivo priming of CTL for adoptive T cell therapy.
- NSV/HIV-1 vector to be used as target cells.
- CD4 T-helper activity the splenocytes are restimulated in vitro with autologous, irradiated, vector transduced
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Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002392010A CA2392010A1 (en) | 1999-08-27 | 2000-08-23 | Use of lentiviral vectors for antigen presentation in dendritic cells |
EP00957722A EP1214437A1 (en) | 1999-08-27 | 2000-08-23 | Use of lentiviral vectors for antigen presentation in dendritic cells |
AU69302/00A AU6930200A (en) | 1999-08-27 | 2000-08-23 | Use of lentiviral vectors for antigen presentation in dendritic cells |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US38471999A | 1999-08-27 | 1999-08-27 | |
US09/384,719 | 1999-08-27 |
Publications (2)
Publication Number | Publication Date |
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WO2001016342A1 WO2001016342A1 (en) | 2001-03-08 |
WO2001016342A9 true WO2001016342A9 (en) | 2002-09-19 |
Family
ID=23518472
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/US2000/023162 WO2001016342A1 (en) | 1999-08-27 | 2000-08-23 | Use of lentiviral vectors for antigen presentation in dendritic cells |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1214437A1 (en) |
AU (1) | AU6930200A (en) |
CA (1) | CA2392010A1 (en) |
WO (1) | WO2001016342A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9598469B2 (en) | 2001-07-05 | 2017-03-21 | Novartis Vaccines And Diagnostics, Inc. | HIV-1 south african subtype C env proteins |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2358385C (en) | 1998-12-31 | 2013-08-06 | Chiron Corporation | Polynucleotides encoding antigenic hiv type c polypeptides, polypeptides and uses thereof |
EP1562635A4 (en) * | 2002-11-07 | 2007-12-19 | Chang Lung Ji | Modified dendritic cells |
CA2611056C (en) * | 2005-06-01 | 2016-06-28 | California Institute Of Technology | Method of targeted gene delivery using viral vectors |
KR20140035537A (en) | 2006-07-21 | 2014-03-21 | 캘리포니아 인스티튜트 오브 테크놀로지 | Targeted gene delivery for dendritic cell vaccination |
RS53257B2 (en) | 2009-07-24 | 2018-06-29 | Immune Design Corp | Lentiviral vectors pseudotyped with a sindbis virus envelope glycoprotein |
US8323662B1 (en) | 2012-03-30 | 2012-12-04 | Immune Design Corp. | Methods useful for generating highly mannosylated pseudotyped lentiviral vector particles comprising a Vpx protein |
DK2831095T3 (en) | 2012-03-30 | 2019-02-18 | Immune Design Corp | LENTIVIRAL VECTOR PARTICLES WITH IMPROVED TRANSDUCTION EFFICIENCY FOR CELL EXPRESSING DC SIGN |
US9713635B2 (en) | 2012-03-30 | 2017-07-25 | Immune Design Corp. | Materials and methods for producing improved lentiviral vector particles |
US9493789B2 (en) * | 2014-04-24 | 2016-11-15 | Miltenyi Biotec Gmbh | Automated generation of genetically modified stem cells |
MX2018015593A (en) | 2016-06-16 | 2019-06-06 | Nuseed Pty Ltd | Elite event canola ns-b50027-4. |
GB202105278D0 (en) * | 2021-04-13 | 2021-05-26 | Imperial College Innovations Ltd | Cell therapy |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
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EP1007716A4 (en) * | 1997-04-17 | 2000-06-14 | Univ California | Use of lentiviral vectors for antigen presentation in dendritic cells |
-
2000
- 2000-08-23 AU AU69302/00A patent/AU6930200A/en not_active Abandoned
- 2000-08-23 CA CA002392010A patent/CA2392010A1/en not_active Abandoned
- 2000-08-23 EP EP00957722A patent/EP1214437A1/en not_active Withdrawn
- 2000-08-23 WO PCT/US2000/023162 patent/WO2001016342A1/en not_active Application Discontinuation
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9598469B2 (en) | 2001-07-05 | 2017-03-21 | Novartis Vaccines And Diagnostics, Inc. | HIV-1 south african subtype C env proteins |
Also Published As
Publication number | Publication date |
---|---|
WO2001016342A1 (en) | 2001-03-08 |
AU6930200A (en) | 2001-03-26 |
EP1214437A1 (en) | 2002-06-19 |
CA2392010A1 (en) | 2001-03-08 |
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