WO2013110150A1 - Formulation vaccinale antitumorale à base de nanotubes de carbone - Google Patents

Formulation vaccinale antitumorale à base de nanotubes de carbone Download PDF

Info

Publication number
WO2013110150A1
WO2013110150A1 PCT/BR2013/000025 BR2013000025W WO2013110150A1 WO 2013110150 A1 WO2013110150 A1 WO 2013110150A1 BR 2013000025 W BR2013000025 W BR 2013000025W WO 2013110150 A1 WO2013110150 A1 WO 2013110150A1
Authority
WO
WIPO (PCT)
Prior art keywords
carbon nanotubes
agonist
acid
antigen
nanotubes according
Prior art date
Application number
PCT/BR2013/000025
Other languages
English (en)
Portuguese (pt)
Inventor
Ricardo Tostes Gazzinelli
Luiz Orlando Ladeira
Clascídia Aparecida FURTADO
Paula Cristina BATISTA DE FARIA GONTIJO
Original Assignee
Universidade Federal De Minas Gerais - Ufmg
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
Priority claimed from BR102012033580A external-priority patent/BR102012033580B1/pt
Application filed by Universidade Federal De Minas Gerais - Ufmg filed Critical Universidade Federal De Minas Gerais - Ufmg
Publication of WO2013110150A1 publication Critical patent/WO2013110150A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6927—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
    • A61K47/6929—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle

Definitions

  • the present invention describes acid nanocarbonised functionalized carbon nanotubes having at least one tumor antigen coupled thereto, preferably from the "cancer / testis" family, their preparation process and their use in antitumor vaccine formulations.
  • at least one Toll-like receptor agonist can be coupled to these carbon nanotubes, which has potent immunostimulatory activity.
  • This vaccination strategy can be used to treat diseases, such as cancer, which require induction of a cell-mediated and antibody-specific immune response.
  • Adjuvants are compounds that enhance the immune response against co-inoculated antigens.
  • a good adjuvant should be stable, ie degradation resistant, low cost, immunologically inert, compatible with different types of antigen, and capable of promoting an appropriate humoral and / or cellular immune response, depending on the need for body protection.
  • Adjuvants based on aluminum salts (alum) are the most widely used in approved vaccine formulations as they provide satisfactory results. However, despite its frequent and global use, the mode of action of this type of adjuvant is not yet well understood (AGUILAR, J. C; RODRIGUEZ; EG Vaccine adjuvants revisited. Vaccine, v. 25, n.19, p. 3752 -3762, 2007; LINDBLAD, EB Aluminum compounds for use in vaccines (Immunology and Celi Biology, v. 82, pp. 497-505, 2004).
  • an adjuvant depends on its ability to effectively deliver antigens to antigen presenting cells (APCs) and thereby activate them.
  • APCs antigen presenting cells
  • Nanotubes An example of a nanometer particle is carbon nanotubes, which have had important implications for the development of nanoformulations for medical and pharmaceutical applications, including biosensors and carrier vehicles. drug delivery.
  • pure carbon nanotubes are inherently hydrophobic. This is the main obstacle to its biological and medicinal use, as solubility is quite low in many aqueous fluid compatible solvents.
  • Nanotube functionalization has been used to manage this problem and in many cases this allows the binding of biologically activated peptides and medicinal drugs to their surface.
  • the most promising protein antigens to induce tumor cell-specific immune response are those of the "cancer / testis" family, which are not expressed in normal cells except testis germ cells - however, these are not recognized by the immune system.
  • the therapeutic potential of this group of tumor antigens has been demonstrated by several studies, for example, VAN PEL, A. et al. Immunological Reviews, v. 145, p. 229-250, 1995; THURNER, B. et al. Journal of Experimental Medicine, v. 190, no. 11, p. 1669-1678, 1999; REYNOLDS, S. R. et al. Clinical Cancer Research, v. 9, p. 657-662, 2003.
  • cancer / testis antigens are still poorly used as immunological targets due to the high heterogeneity in expression of the various members of this family (KIRKIN, AF; DZHAN DZH UGAZYAN, KN; ZEUTHEN, J. Cancer / antigen testing: structural and immunobiological properties Cancer Investigations, v. 20, no. 2, pp. 222-236, 2002; ZENDMAN, AJ; RUITER, DJ; VAN MUIJEN, GNP Cancer / testis-associated genes: Identification, expression profile, and putative function (Journal of Cellular Physiology, v. 194, no. 3, pp. 272-288, 2003).
  • NY-ESO-1 protein is an example of cancer / testis protein. Its function in germ cells and tumor development remains unknown, as is that of most antigens in this family.
  • NY-ESO-1 protein is known as one of the most immunogenic tumor antigens, being found in most tumor types. The frequency of expression in some types, such as melanoma, lung, esophageal cancer, and synovial sarcomas, can reach up to 80% of patients, varying from one individual to another (GNJATIC, S. et al. NY-ESO-1 : review of an immunogenic tumor antigen Advances in Cancer Research, v. 95, pp.
  • the technology presented comes as an alternative to fill the gaps left by the vaccine methods that are used so far.
  • most vaccines have been developed using live, attenuated organisms or pathogen fragments.
  • live or attenuated pathogens can pose a serious risk and result in serious adverse effects, as reported for pertussis and polio vaccines, due to intrinsic instability of organisms and consequently , to the possible return to its virulent form.
  • the presented vaccine formulation utilizes antigenic proteins, or fragments thereof, coupled to carbon nanotubes. Therefore, in terms of safety, it is advantageous over vaccines that use live or attenuated pathogens (DONNELLY, S. et al.
  • Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminum hydroxide in brain Brain, v. 124, no. 9, pp. 1821-1831, 2001; FROST, L. et al., Persistent subcutaneous nodules in children hyposensitized with aluminum-containing allergen extracts, Allergy, v. 40, no. pp. 368-372 (1985). These disorders are significantly reduced with the vaccine formulation proposed in the present invention.
  • the adjuvant activity of the vaccine complex developed in the present technology is characterized by the efficient delivery of the protein antigen, through carbon nanotube, combined with the costimulatory signal of the other molecule.
  • this vaccine system is able to stimulate the immune system more effectively and lasting.
  • PI0510570-6 describes a cancer antigen treatment vaccine which comprises a modified MAGE-3 antigen, a NY-ESO-1 antigen and an adjuvant. It comprises a saponin, QS21, formulated in a cholesterol-containing liposome, and an immunostimulatory oligonucleotide, CpG.
  • the present invention also uses NY-ESO-1 antigen and CpG oligonucleotide as an immunostimulant, it differs from that found in the prior art in that it has such components associated with carbon nanotubes.
  • US2009 / 0246213 deals with a DNA vaccine for developing tumor-specific immunity.
  • Its composition comprises two plasmid expression vectors, each containing a sequence encoding an antigen.
  • the first expression vector contains the sequence of an antigen that is narrowly expressed in tumors, NY-ESO-1, and is recognized by CD4 + helper T cells;
  • the second expression vector contains the sequence of a specific tumor antigen or tumor associated antigen that is recognized by CD8 + cytotoxic T cells and is different from that expressed in the first vector.
  • This technology is different from the present invention, which is based on carbon nanotubes rather than recombinant DNA.
  • CN 1647821 describes a nanovacin constructed by the magnetic ultrasound process.
  • the vaccine is composed of an intracorporeal drug carrier (in this case a biological nanoemulsion), gastric cancer-specific MG7 antigen, and an immunological adjuvant which is a CpG motif-containing oligonucleotide sequence.
  • an intracorporeal drug carrier in this case a biological nanoemulsion
  • gastric cancer-specific MG7 antigen gastric cancer-specific MG7 antigen
  • an immunological adjuvant which is a CpG motif-containing oligonucleotide sequence.
  • it is a stomach cancer-specific vaccine and therefore, unlike the technology presented, it is a vaccine for cancer in general, given the use of NY-ESO-1 protein as an antigen.
  • this protein is expressed in most tumor types.
  • the nanoemulsion reported in CN1647821 is not specifically a carbon nanotube, as in the technology presented.
  • US201 1/0236495 deals with a composition comprising an anticancer nucleic acid sequence encoding UDP-glucuronosyltransferase or p53, non-covalently attached to a nanoparticle, which may be a carbon nanotube.
  • This composition is used for treatment of tumor cells.
  • the difference between this technology and the present invention is in the antigen used.
  • FIG. 1 shows transmission electron microscopy images of the crude multiwall carbon nanotube (MWCNT) sample.
  • Image A of the figure shows a representative overview of the entire sample.
  • Images B and C illustrate in greater detail the presence of metallic impurities (darker spheres) surrounded by graphite layers (B) and tubes of different internal and external diameters (B and C).
  • Figure 2 shows transmission electron microscopy image of the MWCNT sample after severe oxidation.
  • Image A shows a representative overview of the entire sample.
  • Images B and C show, in enlargement, the obtaining of a more free sample of impurities and the presence of carbon nanotubes with defective walls.
  • Figure 3 presents graphs for thermogravimetric analysis of MWCNT samples before and after severe oxidation.
  • a and B show TG curves, while C and D show DTG curves for the crude and oxidized MWCNT samples, respectively.
  • the "position” and “relative area (%)" parameters of the Lorentzian adjustment are shown in the figure.
  • Figure 4 shows the Raman spectra obtained using an excitation wavelength of 514.5 nm from severely oxidized (A.1 and B.1) and crude (A.2 and B.2) MWCNT samples.
  • the spectra show the spectral region of D - band (approximately 1350 cm -1) and G (approximately 1590 cm "1). These spectra were normalized by G. Since the B band spectra show the spectral band G '( approximately 2700 cm -1 ).
  • Figure 5 shows the Raman spectra of samples of oxidized MWCNT (A), ovalbumin (OVA) (B) and MWCNT-OVA (C), in the spectral range between 900 and 2100 cm -1 . 325 nm excitation wave.
  • Figure 6 presents images regarding the evaluation of cell viability in the presence of different MWCNT concentrations by MTT metabolization. Formazan crystals formed (indicated by arrows) are indicative of the presence of viable cells.
  • Image A of the figure represents the negative control with dendritic cells only (without MWCNT).
  • Image B represents the dendritic cell test in the presence of 1 ⁇ g / mL MWCNT.
  • Image C represents the test result in dendritic cells in the presence of 10 ⁇ g / mL MWCNT.
  • Image D represents the test on dendritic cells in the presence of 20 g / ml MWCNT.
  • image E represents the test result in dendritic cells in the presence of 50 ⁇ g / mL MWCNT.
  • Figure 7 presents images, by confocal microscopy, regarding the evaluation of the internalization of the MWCNT-OTI-FITC complex.
  • Dendritic cells are observed after phagocytosis assay, showing presence of fluorescence-labeled peptides coupled inside MWCNTs.
  • Image B shows the FITC-labeled OTI peptide; in image C, the core stained with Dapi; in image D, the Celi Mask ® labeled cytoplasm; in image A, the transmitted image and, lastly, in image E, the overlap of the four images.
  • Figure 8 shows graphs relating to characterization of the immune response induced by MWCNT vaccination.
  • Balb / c animals were immunized with formulations containing OVA antigen coupled to carbon nanotubes.
  • Graph A represents the production of serum IgG Total IgG1, IgG1 and IgG2a antibodies evaluated by ELISA.
  • Graph B represents IFN- ⁇ production after 72 hours of cultivation, quantified by ELISA, obtained from splenocyte assay of immunized animals that were re-stimulated with TCD4 + and TCD8 + OVA-specific peptides.
  • Figure 9 shows graphs for the evaluation of anti-NY-ESO-1 humoral and cellular response induced by carbon nanotube vaccination (MWCNT).
  • MWCNT carbon nanotube vaccination
  • C57BL / 6 animals were immunized with formulations containing NY-ESO-1 coupled to carbon nanotubes.
  • Graph A depicts the production of total IgG, IgG1 and IgG2c anti-NY-ESO-1 antibodies present in animal serum assessed by ELISA.
  • Graph B shows IFN- ⁇ production verified after 72h of culture, ELISA-quantified, obtained from splenocyte assay of immunized animals that were restimulated with specific CD4 + or CD8 + T peptides or the recombinant NY- ESO-1.
  • Graph C represents the result of ELISPOT quantification of IFN- ⁇ producing cells after NY-ESO-1 restimulation of the splenocytes of immunized animals.
  • Figure 10 shows graphs for tumor growth follow-up after MWCNT vaccination.
  • C57BL / 6 animals immunized with NY-ESO-1 antigen and CpG oligonucleotide coupled to carbon nanotubes and their controls were challenged with 5x10 4 B16 melanoma cells expressing NY-ESO-1.
  • graph A tumor growth was followed for 35 days.
  • graph B the animals were also followed for survival percentage after challenge.
  • the symbol ( ⁇ ) means death.
  • Figure 11 shows graphs for evaluation of anti-NY-ESO-1 cell response induced by carbon nanotube therapeutic vaccination (MWCNT) and graphs for follow-up tumor growth follow-up.
  • C57BL / 6 animals were challenged with 5x10 4 B16 melanoma cells expressing NY-ESO-1 and then treated with NY-ESO-1 and CpG oligonucleotide-coupled formulations containing carbon nanotubes and their controls.
  • Graph A represents the production of IFN- ⁇ verified after 72h of culture, quantified by ELISA, obtained from splenocyte assay from treated animals that were restimulated with specific CD4 + or CD8 + T peptides or the recombinant NY- ESO-1.
  • graph B tumor growth was followed for 30 days.
  • graph C the animals were also followed for survival percentage after challenge.
  • Figure 12 shows graphs for tumor growth and mortality follow-up after prophylactic vaccination and carbon nanotube therapy (MWCNT).
  • MWCNT prophylactic vaccination and carbon nanotube therapy
  • the present invention describes acid-oxygenated functionalized multi-walled carbon nanotubes having at least one tumor antigen, such as a cancer / testis family protein, preferably covalently coupled or preferably NY-ESO-1 protein. non-covalently.
  • at least one Toll-like receptor agonist preferably a CpG-derived oligonucleotide may also be coupled to the nanotubes.
  • n 1.
  • Such nanotubes can therefore be used as adjuvants and carriers in antitumor vaccine formulations associated with pharmaceutically and pharmacologically acceptable excipients.
  • Vaccine formulations may be liquid, solid or semi-solid.
  • Excipients may be selected from the group comprising water, saline, phosphate buffered solutions, Ringer's solution, dextrose solution, Hank's solution, biocompatible saline solutions containing or not polyethylene glycol, non-aqueous vehicles such as fixed oils, sesame oil , ethyl oleate or triglycerides, alone or in admixture, including pharmaceutical nanoformulations.
  • the excipients may contain additives such as buffers, preservatives, binders, disintegrants, diluents, lubricants and / or surfactants.
  • the vaccine formulation may be administered by oral, inhalation, dermal, transdermal, intramuscular, intravenous, subcutaneous, intraperitoneal routes or by devices that may be implanted or injected.
  • Example 1 Functionalization of Multiple Wall Nanotubes
  • MWCNT multi-wall carbon nanotubes
  • CVD chemical vapor deposition
  • hydrocarbons such as ethylene
  • inert gas such as argon
  • the pyrolysis process was catalyzed by iron and cobalt oxide nanoparticles anchored to a magnesium oxide support.
  • the obtained MWCNTs are 10-40 nm in diameter and 10-80 ⁇ in length ( Figure 1) (FEDERAL UNIVERSITY OF MINAS GENERAL. Luiz Orlando Ladeira, Gustavo Cat ⁇ o Alves, Sergio de Oliveira. carbon nanostructures (BR No. PI 0404543-2, 02 March 2004).
  • the residue (approximately 12% by weight) is composed of oxidized catalyst metal particles.
  • Figure 3D For the strongly oxidized sample (Figure 3D), an initial loss of approximately 5 wt.% At approximately 150 ° C was characterized for decomposition of organic material (functional groups on the surface).
  • the relative amount of nanotubes in the oxidized sample increased due to the removal of amorphous carbon and metallic residues, going from 32 to 46% by mass in the first decomposition and from 25 to 37% in the second decomposition.
  • the peak of the nanotube degradation temperature decreased relative to the crude sample due to the formation of surface defects in the oxidized tubes (shown in Figure 2C).
  • the percentage corresponding to the residue significantly reduced to approximately 5% by mass. Decompositions observed at higher temperatures, 750 ° C at C and 675 ° C at D, are characteristic of graphite particles.
  • OVA antigen was added to a MilliQ oxidized MWCNT sample dispersion in water. This dispersion was deposited on silicon substrate and Raman scattering of these deposits was investigated to characterize the oxidized MWCNT-protein interaction.
  • the spectra in Figure 5 were obtained using an excitation wavelength of 325 nm.
  • Figure 5A the D (1417 cm -1 ) and G (1584 cm -1 ) bands of oxidized MWCNT are observed. OVA protein bands appear in the same spectral region.
  • Dendritic cells on the tenth day of cultivation, were incubated in an oven at 37 ° C and 5% CO 2 for 24 hours with MWCNTs (1-50 pg / mL) coupled to OVA-OTI peptide (5-100 pg / mL). ) conjugated to FITC.
  • MWCNTs 1-50 pg / mL
  • OVA-OTI peptide 5-100 pg / mL).
  • FITC conjugated to FITC.
  • the cells were labeled, fixed in 4% formaldehyde and then observed by confocal microscopy.
  • the slides were analyzed under a Zeiss 5Live confocal microscope and the images were acquired and formatted by ZEN Light Edition software.
  • Cells from the transgenic B16 melanoma cell line and CT26 colon carcinoma expressing NY-ESO-1 were grown in RPMI supplemented with 10% SFB and penicillin / streptomycin in a 37 ° C, 5% CO 2 greenhouse. 300 pg / ml geneticin was added for maintenance of the expression plasmid.
  • a cell viability assay was carried out by metabolizing the MTT tetrazolic salt by mitochondrial enzymes. It is a sensitive and quantitative colorimetric method that measures cell metabolism, proliferation and activation state (MOSMANN, T. Rapid colorimetric assay for cell growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods, v 65, no. 1-2, pp. 55-63, 1983).
  • DCs Immature dendritic cells on the tenth day of cultivation were placed in contact with different concentrations of multi-walled carbon nanotubes (1, 10, 20 and 50 pg / mL) and kept in greenhouse culture at 37 ° C and 5%. CO 2 .
  • the viability of the DCs was verified and visualized by optical microscopy after 2 hours of culture, from the formation of water insoluble Formazan crystals. Then, an SDS-HCI solution for solubilization of the crystals was added to each well. After 20 hours of culture, the absorbance values of the resulting solution at 595 nm were read on an automatic microplate reader. Cells with 20 pg / mL MWCNTs were 75% viable, assuming 100% for those grown without oxidized carbon nanotubes. Only from 50 pg / mL a significant drop in cell viability was observed (Figure 7).
  • mice In order to characterize the role of MWCNTs in vaccine formulations, as well as the efficiency of non-covalent coupling of antigens to their oxidized surface, Balb / c mice were subjected to a protocol of one to three equivalent immunizations at 15-day intervals. These immunizations were given by the administration of 100 ⁇ l of the subcutaneous vaccine formulation.
  • Each immunizing solution contained 1-50 pg of the properly characterized oxidized MWCNTs for the evaluation of their activity as immunological adjuvants coupled with 5-100 pg of endotoxin-free ovalbumin protein (OVA), whether or not containing 1-100 pg of oligonucleotides.
  • OVA ovalbumin protein
  • CpG derived from Trypanosoma cruzi. Coupling was by sonification for 30 minutes.
  • As a positive control one of the groups was immunized with 30% (v / v) alum, 5-100 pg endotoxin-free OVA and in the presence of CpG oligonucleotides (1-100 pg).
  • Sera from animals submitted to immunizations were collected nine days after the last immunization and were used to evaluate the production of specific anti-OVA antibodies by ELISA.
  • the cellular response induced by the immunization protocol was measured 21 days after the last immunization.
  • mice were immunized with a new formulation containing 5-100 pg of non-adsorbed NY-ESO-1 tumor antigen. covalently by sonification for 30 minutes to the walls of oxidized carbon nanotubes (1-50 pg), with or without the addition of 1-100 pg of Trypanosoma cruzi-derived CpG oligonucleotides. Immunizations were performed at one to three subcutaneous equivalent doses at 21-day intervals.
  • Serum from immunized animals was used to check for the production of anti-NY-ESO-1 specific antibodies (Figure 9A).
  • the cellular response induced by the immunization protocol was measured 21 days after the last immunization ( Figures 9B and 9C). The results show that groups of animals immunized with formulations containing MWCNT-coupled antigens showed better NY-ESO-1 antigen-specific immune response compared to the other groups.
  • mice were challenged with the B16 melanoma or CT26 colon carcinoma cell line expressing the NY-ESO-1 tumor antigen. Each animal received 5x10 4 (B16) or 1x10 6 (CT26) cells, subcutaneously in the posterior dorsal region. Tumor growth was followed twice a week for a period of 90 days. Tumor measurement was given as the area in mm 2 . This data shows that immunization with formulations containing carbon nanotubes were able to retard NY-ESO-1 antigen-specific tumor growth ( Figures 10A and 12B) and increase the life expectancy of animals ( Figures 10B and 12C).
  • mice were challenged and then treated with the formulations containing 5-100 pg of non-covalently adsorbed NY-ESO-1 tumor antigen by sonification for 30 minutes. to the walls of oxidized carbon nanotubes (1-50 g), with or without the addition of 1-100 g of Trypanosoma cruzi derived CpG oligonucleotides. Immunizations were performed at one to three subcutaneous equivalent doses at 7-day intervals beginning on the third day after challenge.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Nanotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente invention concerne des nanotubes de carbone fonctionnalisés avec des groupes oxygénés acides, présentant au moins un antigène tumoral accouplé à ceux-ci, de préférence de la famille "cancer/testis", leur procédé de préparation et leur utilisation dans des formulations vaccinales antitumorales. Par ailleurs, on peut accoupler à ces nanotubes de carbone, au moins un agoniste de récepteurs du type Toll, lequel possède une puissante activité immunostimulatrice. Cette stratégie de vaccination peut être utilisée dans le traitement de maladies telles que le cancer, lesquelles nécessitent l'induction d'une réponse immunitaire médiée tant par des cellules que par des anticorps spécifiques.
PCT/BR2013/000025 2012-01-23 2013-01-22 Formulation vaccinale antitumorale à base de nanotubes de carbone WO2013110150A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
BR1020120014505 2012-01-23
BR102012001450 2012-01-23
BR102012033580A BR102012033580B1 (pt) 2012-12-28 2012-12-28 formulação vacinal antitumoral baseada em nanotubos de carbono e uso
BR1020120335808 2012-12-28

Publications (1)

Publication Number Publication Date
WO2013110150A1 true WO2013110150A1 (fr) 2013-08-01

Family

ID=48872844

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/BR2013/000025 WO2013110150A1 (fr) 2012-01-23 2013-01-22 Formulation vaccinale antitumorale à base de nanotubes de carbone

Country Status (1)

Country Link
WO (1) WO2013110150A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009117616A2 (fr) * 2008-03-19 2009-09-24 Yale University Compositions de nanotubes de carbone et leurs procédés d'utilisation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009117616A2 (fr) * 2008-03-19 2009-09-24 Yale University Compositions de nanotubes de carbone et leurs procédés d'utilisation

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
JUNQUEIRA, C ET AL.: "Trypanosoma cruzi adjuvants potentiate T cell- mediated immunity induced by NY-ESO-1 antitumor vaccine.", PLOS ONE., vol. 7, no. 5, 8 May 2012 (2012-05-08), XP055080240 *
MENG, J ET AL.: "Carbon Nanotubes conjugated to tumor lysate protein enhance the efficacy of an antitumor immunotherapy.", SMALL., vol. 4, no. 9, 8 September 2008 (2008-09-08), pages 1364 - 1370, XP055078490 *
VILLA, HC ET AL.: "Single-walled carbon nanotubes deliver peptide antigen into dendritic cells and enhance IgG responses to tumor- associated antigens.", ACS NANO., vol. 5, no. 7, 26 July 2011 (2011-07-26), pages 5300 - 5311, XP055078492 *

Similar Documents

Publication Publication Date Title
Hassan et al. Dual stimulation of antigen presenting cells using carbon nanotube-based vaccine delivery system for cancer immunotherapy
Gong et al. Proton-driven transformable nanovaccine for cancer immunotherapy
Hassan et al. Application of carbon nanotubes in cancer vaccines: Achievements, challenges and chances
Liu et al. Structure-based programming of lymph-node targeting in molecular vaccines
Faria et al. Oxidized multiwalled carbon nanotubes as antigen delivery system to promote superior CD8+ T cell response and protection against cancer
Zhao et al. The application of self-assembled nanostructures in peptide-based subunit vaccine development
Hassan et al. Carbon nanotubes' surface chemistry determines their potency as vaccine nanocarriers in vitro and in vivo
Cao et al. Photothermally controlled MHC class I restricted CD8+ T‐cell responses elicited by hyaluronic acid decorated gold nanoparticles as a vaccine for cancer immunotherapy
Han et al. Ferritin protein cage nanoparticles as versatile antigen delivery nanoplatforms for dendritic cell (DC)-based vaccine development
Skwarczynski et al. Peptide-based subunit nanovaccines
Thomann et al. Antitumor activity of liposomal ErbB2/HER2 epitope peptide-based vaccine constructs incorporating TLR agonists and mannose receptor targeting
Zhou et al. Just-in-time vaccines: Biomineralized calcium phosphate core-immunogen shell nanoparticles induce long-lasting CD8+ T cell responses in mice
Battigelli et al. Carbon nanomaterials as new tools for immunotherapeutic applications
Wang et al. Alum-functionalized graphene oxide nanocomplexes for effective anticancer vaccination
US12016910B2 (en) Antigenic peptides for prevention and treatment of cancer
Geary et al. Diaminosulfide based polymer microparticles as cancer vaccine delivery systems
KR20140037789A (ko) 암의 예방 및 치료를 위한 조성물 및 방법
JP7331207B2 (ja) 癌治療のための免疫原性化合物
Azevedo et al. Advances in carbon nanomaterials for immunotherapy
Fujita et al. Nanoparticle-based peptide vaccines
Huang et al. Quaternized cationic carbon dots as antigen delivery systems for improving humoral and cellular immune responses
Alharbi et al. The influence of component structural arrangement on peptide vaccine immunogenicity
EP3220913A1 (fr) Nouveau vaccin à base de nanoparticules ciblant des antigènes du cancer du testicule (cta) et son utilisation dans le cadre de tumeurs malignes solides et hématologiques
US20190388532A1 (en) Immunogenic Compounds For Cancer Therapy
WO2013110150A1 (fr) Formulation vaccinale antitumorale à base de nanotubes de carbone

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13741025

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13741025

Country of ref document: EP

Kind code of ref document: A1