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rWTC-MBTA Vaccine Induces Potent Adaptive Immune Responses Against Glioblastomas via Dynamic Activation of Dendritic Cells.
Wang, Herui; Medina, Rogelio; Ye, Juan; Zhang, Yaping; Chakraborty, Samik; Valenzuela, Alex; Uher, Ondrej; Hadrava Vanova, Katerina; Sun, Mitchell; Sang, Xueyu; Park, Deric M; Zenka, Jan; Gilbert, Mark R; Pacak, Karel; Zhuang, Zhengping.
Afiliación
  • Wang H; Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 10022, USA.
  • Medina R; Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 10022, USA.
  • Ye J; Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 10022, USA.
  • Zhang Y; Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 10022, USA.
  • Chakraborty S; NE1 Inc., New York, NY, 10022, USA.
  • Valenzuela A; Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 10022, USA.
  • Uher O; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
  • Hadrava Vanova K; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
  • Sun M; Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 10022, USA.
  • Sang X; Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 10022, USA.
  • Park DM; John Theurer Cancer Center, HUMC, Hackensack Meridian School of Medicine, 92 2nd St, Hackensack, NJ, 07601, USA.
  • Zenka J; Department of Medical Biology, Faculty of Science, University of South Bohemia, Ceské Budejovice, 37005, Czech Republic.
  • Gilbert MR; Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 10022, USA.
  • Pacak K; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
  • Zhuang Z; Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 10022, USA.
Adv Sci (Weinh) ; 11(14): e2308280, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38298111
ABSTRACT
Despite strides in immunotherapy, glioblastoma multiforme (GBM) remains challenging due to low inherent immunogenicity and suppressive tumor microenvironment. Converting "cold" GBMs to "hot" is crucial for immune activation and improved outcomes. This study comprehensively characterized a therapeutic vaccination strategy for preclinical GBM models. The vaccine consists of Mannan-BAM-anchored irradiated whole tumor cells, Toll-like receptor ligands [lipoteichoic acid (LTA), polyinosinic-polycytidylic acid (Poly (IC)), and resiquimod (R-848)], and anti-CD40 agonistic antibody (rWTC-MBTA). Intracranial GBM models (GL261, SB28 cells) are used to evaluate the vaccine efficacy. A substantial number of vaccinated mice exhibited complete regression of GBM tumors in a T-cell-dependent manner, with no significant toxicity. Long-term tumor-specific immune memory is confirmed upon tumor rechallenge. In the vaccine-draining lymph nodes of the SB28 model, rWTC-MBTA vaccination triggered a major rise in conventional dendritic cell type 1 (cDC1) 12 h post-treatment, followed by an increase in conventional dendritic cell type 2 (cDC2), monocyte-derived dendritic cell (moDC), and plasmacytoid dendritic cell (pDC) on Day 5 and Day 13. Enhanced cytotoxicity of CD4+ and CD8+ T cells in vaccinated mice is verified in co-culture with tumor cells. Analyses of immunosuppressive signals (T-cell exhaustion, myeloid-derived suppressor cells (MDSC), M2 macrophages) in the GBM microenvironment suggest potential combinations with other immunotherapies for enhanced efficacy. In conclusion, the authors findings demonstrate that rWTC-MBTA induces potent and long-term adaptive immune responses against GBM.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas / Glioblastoma Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas / Glioblastoma Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania