ES2627233T3 - Nanotecnología de vacunas - Google Patents

Nanotecnología de vacunas Download PDF

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Publication number
ES2627233T3
ES2627233T3 ES13156642.4T ES13156642T ES2627233T3 ES 2627233 T3 ES2627233 T3 ES 2627233T3 ES 13156642 T ES13156642 T ES 13156642T ES 2627233 T3 ES2627233 T3 ES 2627233T3
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Spain
Prior art keywords
virus
nanotransporter
lymphocyte antigen
immunostimulatory agent
poly
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ES13156642.4T
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English (en)
Inventor
Ulrich H Von Andrian
Omid C Farokhzad
Robert S Langer
Tobias Junt
Elliott Ashley Moseman
Liangfang Zhang
Pamela Basto
Matteo Iannacone
Frank Alexis
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Harvard College
Brigham and Womens Hospital Inc
Childrens Medical Center Corp
Massachusetts Institute of Technology
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Harvard College
Brigham and Womens Hospital Inc
Childrens Medical Center Corp
Massachusetts Institute of Technology
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Publication of ES2627233T3 publication Critical patent/ES2627233T3/es
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Abstract

Un nanotransportador que comprende: un agente inmunoestimulador, en donde el agente inmunoestimulador es un agonista del receptor de tipo toll; un antígeno de linfocitos T; y, un polímero seleccionado entre el grupo que consiste en: poli(ácido láctico) (PLA), poli(ácido glicólico) (PGA) y poli(ácido láctico/ácido glicólico) (PLGA); en donde el nanotransportador tiene un diámetro medio geométrico comprendido entre 50 nm y 500 nm; en donde el agente inmunoestimulador está unido covalentemente al nanotransportador o el agente inmunoestimulador está unido covalentemente a un polímero a partir del que se forma el nanotransportador, y el antígeno de linfocitos T está encapsulado en el interior del nanotransportador o el antígeno de linfocitos T está unido covalentemente al nanotransportador.

Description

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resto de direccionamiento está conjugado covalentemente con un polímero.
En algunos aspectos, se proporciona una composición que comprende un nanotransportador que se dirige a una célula, tejido u órgano específico y modula una respuesta inmunitaria que comprende un antígeno de linfocitos B
5 sobre su superficie a una densidad que activa los linfocitos B y un agente inmunoestimulador. En algunas realizaciones, el nanotransportador comprende además un resto de direccionamiento. En algunas realizaciones, la composición es una composición farmacéutica y comprende además un transportador farmacéuticamente aceptable. En algunas realizaciones, la composición farmacéutica es una composición de vacuna.
En algunos aspectos, se proporciona una composición, tal como una composición farmacéutica, que comprende un resto de direccionamiento de células presentadoras de antígenos y un nanotransportador. En algunas realizaciones, el resto de direccionamiento de células presentadoras de antígenos y el nanotransportador están conjugados. En algunas realizaciones, el conjugado es un conjugado covalente. En algunas realizaciones, el conjugado es un conjugado no covalente.
15 En algunos aspectos, se proporciona una composición, tal como una composición farmacéutica, que comprende un agente inmunoestimulador y un nanotransportador.
En algunas realizaciones, el antígeno de linfocitos B es una proteína o péptido. En algunas realizaciones, el antígeno de linfocitos B es un antígeno no proteico (es decir, no una proteína o péptido). En algunas realizaciones, la proteína
o péptido es de un agente infeccioso. En algunas realizaciones, el agente infeccioso es una bacteria, hongo, virus, protozoo, o parásito. En algunas realizaciones, el virus es un virus de la viruela, el virus de la viruela, virus del Ébola, virus de Marburg, virus del dengue, virus de la gripe, virus paragripal, virus respiratorio sincitial, virus de la rubéola, virus de la inmunodeficiencia humana, virus del papiloma humano, virus de la varicela-zóster, virus del herpes
25 simple, citomegalovirus, virus de Epstein-Barr, JC virus, rabdovirus, rotavirus, rinovirus, adenovirus, virus del papiloma, parvovirus, picornavirus, poliovirus, virus que producen paperas, virus que producen rabia, reovirus, virus de la rubéola, togavirus, ortomixovirus, retrovirus, hepadnavirus, coxsackievirus, virus de la encefalitis equina, virus de la encefalitis japonesa, virus de la fiebre amarilla, virus de la fiebre del Valle del Rift, virus de la hepatitis A, virus de la hepatitis B, virus de la hepatitis C, virus de la hepatitis D, o virus de la hepatitis E.
En algunas realizaciones, el antígeno de linfocitos B es una molécula pequeña. En algunas realizaciones, la molécula pequeña es una sustancia que crea dependencia, una sustancia adictiva, o una toxina.
En algunas realizaciones, el antígeno de linfocitos B es una sustancia adictiva. En algunas realizaciones, la 35 sustancia adictiva es nicotina, un narcótico, un alucinógeno, un estimulante, un supresor de la tos, un tranquilizante,
o un sedante. En algunas realizaciones, el antígeno de linfocitos B es un opioide o benzodiacepina.
En algunas realizaciones, el antígeno de linfocitos B es una toxina. En algunas realizaciones, la toxina es de un arma química. En algunas realizaciones, la toxina de un arma química es toxina botulínica o fosfeno. Las toxinas de un arma química incluyen también, pero sin limitación, O-Alquilo (<C10, incl. cicloalquil) alquilo (Me, Et, n-Pr o i-Pr)fosfonofluoridatos (por ejemplo, Sarín: O-Isopropil metilfosfonofluoridato, Soman: O-Pinacolil metilfosfonofluoridato), O-Alquilo (<C10, incl. cicloalquilo) N,N-dialquilo (Me, Et, n-Pr o i-Pr) fosforamidocianidatos (por ejemplo, Tabun: O-Etil N,N-dimetilfosforamidocianidato), O-Alquilo (H o <C10, incl. cicloalquilo) S-2-dialquilo (Me, Et, n-Pr o i-Pr)aminoetil alquilo (Me, Et, n-Pr o i-Pr) fosfonotiolatos y las sales alquiladas o protonadas correspondientes (por
45 ejemplo, VX: O-Etil S-2-diiso-propilaminoetil metilfosfonotiolato), Mostazas de azufre: Sulfuro de 2cloroetilclorometilo, Gas mostaza: sulfuro de Bis(2-cloroetilo), Bis(2-cloroetiltio)metano, Sesquimostazas: 1,2-Bis(2cloroetltio)etano, 1,3-Bis(2-cloroetiltio)-n-propano, 1,4-Bis(2-cloroetiltio)-n-butano, 1,5-Bis(2-cloroetiltio)-n-pentano, Bis(2-cloroetiltiometil)éter, Mostaza O: Bis(2-cloroetiltioetil)éter, Lewisites: Lewisite 1: 2-Clorovinildicloroarsina, Lewisite 2: Bis(2-clorovinil)cloroarsina, Lewisite 3: Tris(2-clorovinil)arsina, Mostazas de nitrógeno: HN1: Bis(2cloroetil)etilamina, HN2: Bis(2-cloroetil)metilamina, HN3: Tris(2-cloroetil)amina, Saxitoxina, Ricina, Amiton: O,O-Dietil S-(2-(dietilamino)etil)fosforotiolato y las sales alquiladas o protonadas correspondientes, PFIB: 1,1,3,3,3-Pentafluoro2-(trifluorometil)-1-propeno, 3-Quinuclidinil bencilato (BZ), Fosgeno: Dicloruro de carbonilo, Cloruro de cianógeno, Cianuro de hidrógeno y Cloropicrina: Tricloronitrometano. En algunas realizaciones, la toxina para la inclusión en un nanotransportador es la molécula completa de cualquiera de las anteriores o una parte de la misma.
55 En algunas realizaciones, el antígeno de linfocitos B es un riesgo biológico o agente peligroso para el medio ambiente. En algunas realizaciones, el agente peligroso para el medio ambiente es arsénico, plomo, mercurio, cloruro de vinilo, bifenilos policlorados, benceno, hidrocarburos aromáticos policíclicos, cadmio, benzo(a)pireno, benzo(b)fluoranteno, cloroformo, diclor-difenil-tricloretileno (DDT), P,P’-, aroclor 1254, aroclor 1260, dibenzo(a,h)antraceno, tricloroetileno, dieldrina, cromo hexavalente, o p,p’-diclorodifenildicloroeteno (DDE, P,P’).
En algunas realizaciones, el antígeno de linfocitos B es un hidrato de carbono. En algunas realizaciones, el hidrato de carbono es de un agente infeccioso. En algunas realizaciones, el agente infeccioso es una bacteria, hongo, virus, protozoo, o parásito. En algunas realizaciones, la bacteria es una bacteria de Pseudomonas, Pneumococcus, E. coli, 65 Staphylococcus, Streptococcus, Treponema, Borrelia, Chlamydia, Haemophilus, Clostridium, Salmonella, Legionella, Vibrio o Enterococci bacteria o un Mycobacterium. En algunas realizaciones, el virus es un virus de la viruela, el virus
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