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WO1995027508A1 - Composition utilisable pour induire une reponse immunitaire - Google Patents

Composition utilisable pour induire une reponse immunitaire Download PDF

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Publication number
WO1995027508A1
WO1995027508A1 PCT/AU1995/000206 AU9500206W WO9527508A1 WO 1995027508 A1 WO1995027508 A1 WO 1995027508A1 AU 9500206 W AU9500206 W AU 9500206W WO 9527508 A1 WO9527508 A1 WO 9527508A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
antigen
omp
liposomes
immune response
Prior art date
Application number
PCT/AU1995/000206
Other languages
English (en)
Inventor
James Chin
Original Assignee
The Minister For Agriculture For The State Of New South Wales
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Minister For Agriculture For The State Of New South Wales filed Critical The Minister For Agriculture For The State Of New South Wales
Priority to AU22089/95A priority Critical patent/AU2208995A/en
Publication of WO1995027508A1 publication Critical patent/WO1995027508A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
    • A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55577—Saponins; Quil A; QS21; ISCOMS
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to a novel composition which can be used to raise an immune response in animals. Further, the present invention relates to methods of using this composition.
  • GALT gut associated lymphoid tissue
  • the skin on the other hand, is readily accessible and forms an important barrier between the environment and the body. It is believed to play a role as a primary lymphatic organ because component cells such as keratinocytes and Langerhans cells are not only able to process and present antigens, but are also involved in the production of cytokines and cellular adhesins. Exposure to antigens in the skin usually generates an immune response which is characterised by the recruitment of leukocytes to the inflammatory site.
  • IgA deposition in the epidermis Several examples of abnormal pathology in human skin disorders have reported IgA deposition in the epidermis.
  • Pseudomonas aeruginosa is an opportunistic pathogen of both humans and animals. This bacterium proliferates rapidly in the wet fleece micro environment on the skin of sheep during periods of sustained rain. It causes an inflammatory exudative dermatitis referred to colloquially as "fleecerot".
  • a vaccine for fleecerot based on outer membrane proteins (OMPs) of P. aeruginosa prepared by organic phase partitioning was developed. While in the process of testing various adjuvant formulations for the delivery of this vaccine, the present inventor discovered that it was possible to stimulate a low but detectable pulse of serum IgA that was specifically directed against P. aeruginosa OMP.
  • an ISCO -based formulation was developed which the present inventor was able to demonstrate not only elicited a transitory pulse of serum IgA but also the production of IgA in respiratory tract washings following intra-dermal administration.
  • the present invention consists in a composition for use in raising a cellular and/or humoral immune response in mammals to an antigen, the composition comprising the antigen entrapped within liposomes, the liposomes being integrated into an ISCOM.
  • the liposomes are formed using N-[l-(2,3-
  • DOTAP Dioleoyloxy)propal]-N,N,N-trimethyl-ammoniummethylsulfate
  • the antigen in either native or subunit form
  • the antigen is derived from an organism involved in infection of the skin, respiratory tract, genitourinary tract or other mucosal surface.
  • the organism is a bacteria, fungi, mycoplasma or virus.
  • the ISCOM is composed of matrix of Quil A and cholesterol and preferably an additional lipid such as phosphatidyl choline in a molar ratio. More information regarding ISCOMs may be found in Morein, Veterinary
  • liposomes may be found in G Gregoriadif, 1993, Liposome Technology 2 nd Edition, CRC Press, Boca Raton FL, USA Vol I, II, III. The disclosure of this reference is incorporated herein by reference.
  • the present invention consists in a method for increasing the immune response in a mammal to an antigen comprising administering to the mammal the composition of the first aspect of the present invention.
  • the composition may be administered via a number of routes including intradermal, intratracheal, intranasally, orally, rectally and intravaginally or by douche.
  • Figure 1 shows serum antibody response to OMP
  • Figure 2 shows antibody response to OMP in RTW
  • Figure 3 shows serum antibody response to OMP
  • Figure 4 shows antibody response to OMP in RTW
  • Figure 5 shows MHC class 1 restricted cytotoxicity against ovalbumin in spleen cells from mice previously vaccinated intradermally with SAMA4-0va
  • Figure 6a shows change in spleen size following immunization by different routes
  • Figure 6b shows relative change in lymphocyte subpopulations of the spleen following immunization by different routes
  • Figure 7 shows effect of immunization route on changes in CD3-/B220+ subpopulation in different organ compartments at different times post-vaccination
  • Figure 8 shows effect of immunization route on changes in CD3+/B220+ subpopulation in different organ compartments at different times post-vaccination
  • Figure 9 shows effect of immunization route on changes in CD3+/CD4+ subpopulation in different organ compartments at different times post-vaccination
  • Figure 10 shows effect of immunization route on changes in CD3+/CD8+ subpopulation in different organ compartments at different times post-vaccination.
  • Figure 11 shows effect of immunization route on changes in non-T and non-B subpopulation in different organ compartments at different times post-vaccination.
  • OMPs were purified by organic phase partitioning using chloroform-methanol extraction of a total membrane vesicle preparation. Hydrophobic membrane proteins located as a turbid band at the organic-aqueous interphase were removed and resolubilized in a small volume of glacial acetic acid and this was further diluted with an equal volume of HSM1[ (HS:25mM HEPES pH 7.4, 0.15 M saline) and (Ml:0.5% w/v MegalO]. The mixture was then dialysed at room temperature against HSM2 [HS containing 0.1%
  • the proteiri concentration in the OMP preparation was adjusted to 20mg/ml in HSM2. A 200 ⁇ l aliquot was removed and added to an equal volume of DOTAP 50 ⁇ g in 200 ⁇ l HSM2) . The mixture was sonicated for 5 min with cooling and then used directly to deliver membrane proteins into immune stimulating complexes or ISCOMS. Preparation of SAMA4 OMP vaccine as ISCOSOMES
  • ISCOSOME vaccine or hybrid liposome-ISCOMS were prepared by diluting the liposome antigen complex with HS to a volume of 2.5 ml followed by the addition of 250 ⁇ l of MegalO (2% w/v); 25 ⁇ l phosphatidylcholine (lOmg/ml); 25 ⁇ l cholesterol (10 mg/ml); 40 ⁇ l 5% w/v Quil A. The mixture was rotated overnight at 21°C and dialysed against three changes of PBS. The final protein concentration of the dialysate was adjusted with PBS to a final concentration of 1 mg/ml OMP. Experimental design, intradermal inoculation and intratracheal challenge
  • Intradermal injections were given at 5 sites along the mid-backline with 100 ⁇ g/100 ⁇ l of OMP adjuvanted in
  • Controls Data not presented here, show that sheep given OMP by the ID or IT route without SAMA4 , do not promote significant IgA responses in RTW or blood.
  • the level of IgGl in RTW and blood is significantly less than that elicited by treatment with OMP+SAMA4.
  • Primary ID-IT Response A peak serum IgGl response against OMP was detected on Day 21 after 2 weekly intradermal inoculations with SAMA4+OMP.
  • a pulse of IgA activity also occurred between Days 10 -0 14 while the IgM response peaked at Day 10 and gradually subsided over the next 40 - 50 days.
  • IgG2 activity rose slowly and peaked between Days 20 - 24, and declined gradually over the next 3 months (Fig.l) .
  • IgA and IgGl activity in RTW peaked twice on Days 10 and 20 after ID inoculation at Days 0 and 7 respectively.
  • a small rise in RTW IgM activity was detectable but not IgG2 (Fig. 2)
  • the peptide is processed by the cell and presented on the surface in association with MHC Class 1 and the target cell will then be amenable to lysis by cytotoxic T cells specific for the Ova peptide.
  • a second option is to transfeet the EL4 cell line with a plasmid that encodes the Ova peptide under the control of a eukaryote promoter.
  • G7 is an example of such as cell line which continuously expresses the Ova peptide. G7 was kindly provided for by Dr F Carbone from Monash University.
  • effector cells were set up in cytotoxic assays against chromium labelled targets (T) at various E:T ratios from 90 to 10:1.
  • EL4 was used as a control and a histo- incompatible cell line YAC was used to monitor non ⁇ specific killing.
  • cytotoxic T cells were generated only in mice immunised with SAMA4 adjuvanted ovalbumin. These effectors were specific in killing both EL4+0va peptide and G7 expressing the Ova determinant. Cytotoxicity against EL4 and YAC targets were not detected. Neither SAMA4 vaccinated mice or mice given only ovalbumin produce Ova-specific cytotoxic T cells . It is clear from these results that intradermal delivery of SAMA4 adjuvanted antigens such as ovalbumin is very effective in generating cytotoxic T cell responses in mice.
  • SAMA4 Unlike other oil-based adjuvants that are immiscible and viscous, antigens complexed in SAMA4 retain their aqueous composition and can be easily injected or instilled in alternative orifices.
  • the versatility of SAMA4 was assessed by intranasal (IN) instillation and intragastric (IG) intubation. As shown in Fig. 6, one of the most prominent changes noted in mice subjected to various route treatments is an enlarged spleen. Intradermal injection of a similar amount of SAMA4+bacterial membrane protein (BMP) promoted by far, the greatest enlargement in spleen weight compared to either intranasal or intragastric routes of administration.
  • BMP bacterial membrane protein
  • Fig. 7 shows that between 3-4 days post vaccination, 6-8 fold changes were noted in the composition of the CD3-/B220+ subpopulation of the thymus in ID and IN vaccinated mice.
  • the CD3- marker designates immature lymphocytes, as are most thymocytes.
  • the appearance of the B220+ marker signifies that many of these cells have become activated as a consequence of vaccination since the B220 antigen is also accepted as a marker for cellular activation. This cell population was not up-regulated in the liver, lung or spleen.
  • the percentage of mature (CD3+) and activated (B220+) lymphocytes in the thymus was significantly elevated in mice given vaccine intradermally compared to other routes of inoculation (Fig. 8) .
  • Fig. 9 shows that one of the consequences of vaccination was a down regulation in the number of resident helper T cells bearing the
  • the extent of suppression in this subpopulation was more noticeable in IN and IG treated mice compared to ID vaccinees.
  • the generation of cytotoxic T cells (CD3+/CD8+) is depicted in Fig. 10 and shows that the intranasal route of inoculation was most effective in stimulating a 3-4 fold increase in this subpopulation in the liver.
  • the IG route was also effective in stimulating an increase in cytotoxic T cells in the liver but not the ID route.
  • the change in non-T/non-B lymphocytes in various compartments is summarised in Fig. 11.
  • the ID route was most effective in stimulating by more than 200%, an increase in cells in the thymus.
  • SAMA4 is not only capable of altering trafficking patterns but also the transit frequencies of both lymphocytes and non-lymphocytes (eg. Neutrophils and granulocytes) in various organ compartments. More specifically, these changes are dependent upon the route of administration of SAMA4 adjuvanted antigens.
  • the present inventor has developed a composition which following intradermal administration is able to provide IgGl and IgA responses in serum and in the respiratory tract. Further, as the composition of the present invention does not include an oil-based adjuvant there is no inflammatory reaction. Accordingly, the composition of the present invention is extremely useful in stimulating mucosal immunity. It is therefore believed that the composition of the present invention may be beneficially used in the treatment or prevention of a number of diseases in man such as skin immune disorders (e.g. melanoma, atopic dermatitis, psoriasis), urogenital tract infection (e.g. Candida, sexually transmitted diseases), upper and lower respiratory tract infection (e.g.
  • skin immune disorders e.g. melanoma, atopic dermatitis, psoriasis
  • urogenital tract infection e.g. Candida, sexually transmitted diseases
  • upper and lower respiratory tract infection e.g.
  • influenza mycoplasma, whooping cough, T.B.
  • diseases of the gut e.g. parasitic diseases, salmonella, cholera
  • systemic infections e.g. malaria

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dispersion Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Cette invention concerne une composition destinée à être utilisée pour induire chez des mammifères une réponse immunitaire cellulaire et/ou humorale (mucosique et systèmique) contre un antigène. Cette composition est formée de l'antigène piégé dans des liposomes qui sont eux-mêmes incorporés dans un complexe de stimulation immunitaire (ISCOM). Les liposomes sont de préférence formés avec du N-[1-(2,3-Dioléoyloxy)propal]-N,N,N-triméthyl-ammoniumméthylsulfate (DOTAP). Ces compositions peuvent être administrées par diverses voies telles que les voies intradermique, intratrachéale, intranasale, orale, rectale ou encore par irrigation.
PCT/AU1995/000206 1994-04-12 1995-04-12 Composition utilisable pour induire une reponse immunitaire WO1995027508A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU22089/95A AU2208995A (en) 1994-04-12 1995-04-12 Composition for use in raising an immune response

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPM5004 1994-04-12
AUPM5004A AUPM500494A0 (en) 1994-04-12 1994-04-12 Composition for use in increasing mucosal immunity

Publications (1)

Publication Number Publication Date
WO1995027508A1 true WO1995027508A1 (fr) 1995-10-19

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AU (2) AUPM500494A0 (fr)
WO (1) WO1995027508A1 (fr)
ZA (1) ZA953027B (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997049423A3 (fr) * 1996-06-24 1998-02-19 Yissum Res Dev Co Composition de vaccin contre la grippe encapsulee dans des liposomes et leur procede de fabrication
WO2008077413A1 (fr) 2006-12-22 2008-07-03 Soluciones Biotecnologicas Innovacion Ltda Vaccins adn pour poissons
US7713942B2 (en) 2001-04-04 2010-05-11 Nordic Vaccine Technology A/S Cage-like microparticle complexes comprising sterols and saponins for delivery of polynucleotides
EP2755680A4 (fr) * 2011-09-12 2015-04-15 Pds Biotechnology Corp Formulations vaccinales particulaires
US11612652B2 (en) 2015-11-13 2023-03-28 Pds Biotechnology Corporation Lipids as synthetic vectors to enhance antigen processing and presentation ex-vivo in dendritic cell therapy
US11801257B2 (en) 2008-04-17 2023-10-31 Pds Biotechnology Corporation Stimulation of an immune response by enantiomers of cationic lipids
US11904015B2 (en) 2012-09-21 2024-02-20 Pds Biotechnology Corporation Vaccine compositions and methods of use
US11911359B2 (en) * 2007-03-22 2024-02-27 Pds Biotechnology Corporation Stimulation of an immune response by cationic lipids
US12201685B2 (en) 2012-06-15 2025-01-21 Pds Biotechnology Corporation Methods of modulating immune responses with cationic lipid vaccine compositions

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2066203A (en) * 1979-12-27 1981-07-08 Human Oltoanyagtermelo Adjuvant particles compositions containing said particles and biologically active substances adsorbed thereon and a process for the preparation thereof
AU3403084A (en) * 1983-10-10 1985-04-18 Biotechnology Australia Proprietary Limited Vaccine derived from pseudomonas aeruginosa
EP0180564A2 (fr) * 1984-11-01 1986-05-07 Bror Morein Complexe immunogénique, procédé de préparation et son utilisation comme immunostimulant, vaccins et réactifs
EP0231039A1 (fr) * 1986-01-14 1987-08-05 De Staat Der Nederlanden Vertegenwoordigd Door De Minister Van Welzijn, Volksgezondheid En Cultuur Procédé de préparation de complexes immunologiques et composition pharmaceutique les contenant
WO1990003184A1 (fr) * 1988-09-30 1990-04-05 Bror Morein Matrice a activite immunomodulatrice
WO1992006710A1 (fr) * 1990-10-23 1992-04-30 De Staat Der Nederlanden Vertegenwoordigd Door De Minister Van Welzijn Volksgezondheid En Cultuur Complexes immunogenes, notamment des iscomes
AU3467193A (en) * 1991-12-17 1993-07-19 Regents Of The University Of California, The Gene therapy for cystic fibrosis transmembrane conductance regulator activity (CFTR)

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2066203A (en) * 1979-12-27 1981-07-08 Human Oltoanyagtermelo Adjuvant particles compositions containing said particles and biologically active substances adsorbed thereon and a process for the preparation thereof
AU3403084A (en) * 1983-10-10 1985-04-18 Biotechnology Australia Proprietary Limited Vaccine derived from pseudomonas aeruginosa
EP0180564A2 (fr) * 1984-11-01 1986-05-07 Bror Morein Complexe immunogénique, procédé de préparation et son utilisation comme immunostimulant, vaccins et réactifs
EP0231039A1 (fr) * 1986-01-14 1987-08-05 De Staat Der Nederlanden Vertegenwoordigd Door De Minister Van Welzijn, Volksgezondheid En Cultuur Procédé de préparation de complexes immunologiques et composition pharmaceutique les contenant
WO1990003184A1 (fr) * 1988-09-30 1990-04-05 Bror Morein Matrice a activite immunomodulatrice
WO1992006710A1 (fr) * 1990-10-23 1992-04-30 De Staat Der Nederlanden Vertegenwoordigd Door De Minister Van Welzijn Volksgezondheid En Cultuur Complexes immunogenes, notamment des iscomes
AU3467193A (en) * 1991-12-17 1993-07-19 Regents Of The University Of California, The Gene therapy for cystic fibrosis transmembrane conductance regulator activity (CFTR)

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY, 10, (1988), MOREIN B and LOEUGREN K., "The Requirement of Lipids for the Formation of Immunostimulating Complexes (Iscoms)", pages 161-172. *
CHEMICAL ABSTRACTS, Volume 108, No. 1, issued 4 January 1988, MOREIN B. et al., "The ISCOM: an Immunostimulating Complex", page 422, Abstract No. 4322c. *
INFECTION AND IMMUNITY, Vol. 56, No. 2, February 1988, KERSTEN et al., "Incorporation of the Major Outer Membrane Protein of Neisseria Gonorrhoeae in Saponin-Lipid Complexes", pages 432-438. *
INFECTION AND IMMUNITY, Vol. 56, No. 6, June 1988, KERSTEN et al., "Immunogenicity of Liposomes and Iscoms Containing the Major Outer Membrane Protein of Neisseria Gonorrhoeae", pages 1661-1664. *
VETERINARY MICROBIOLOGY, 23, (1990), MOREIN B., "ISCOMS", pages 79-84. *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997049423A3 (fr) * 1996-06-24 1998-02-19 Yissum Res Dev Co Composition de vaccin contre la grippe encapsulee dans des liposomes et leur procede de fabrication
US7713942B2 (en) 2001-04-04 2010-05-11 Nordic Vaccine Technology A/S Cage-like microparticle complexes comprising sterols and saponins for delivery of polynucleotides
WO2008077413A1 (fr) 2006-12-22 2008-07-03 Soluciones Biotecnologicas Innovacion Ltda Vaccins adn pour poissons
US11911359B2 (en) * 2007-03-22 2024-02-27 Pds Biotechnology Corporation Stimulation of an immune response by cationic lipids
US11801257B2 (en) 2008-04-17 2023-10-31 Pds Biotechnology Corporation Stimulation of an immune response by enantiomers of cationic lipids
EP2755680A4 (fr) * 2011-09-12 2015-04-15 Pds Biotechnology Corp Formulations vaccinales particulaires
US12201685B2 (en) 2012-06-15 2025-01-21 Pds Biotechnology Corporation Methods of modulating immune responses with cationic lipid vaccine compositions
US11904015B2 (en) 2012-09-21 2024-02-20 Pds Biotechnology Corporation Vaccine compositions and methods of use
US11911465B2 (en) 2012-09-21 2024-02-27 Pds Biotechnology Corporation Vaccine compositions and methods of use
US11612652B2 (en) 2015-11-13 2023-03-28 Pds Biotechnology Corporation Lipids as synthetic vectors to enhance antigen processing and presentation ex-vivo in dendritic cell therapy
US11638753B2 (en) 2015-11-13 2023-05-02 PDS Biotechnology Corporalion Lipids as synthetic vectors to enhance antigen processing and presentation ex-vivo in dendritic cell therapy

Also Published As

Publication number Publication date
AU2208995A (en) 1995-10-30
AUPM500494A0 (en) 1994-05-05
ZA953027B (en) 1996-02-19

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