TY - JOUR
T1 - Multifunctional Nanovaccine Sensitizes Breast Cancer to Immune Checkpoint Therapy
AU - Peres, Carina
AU - Matos, Ana I.
AU - Carreira, Bárbara
AU - Moura, Liane I.F.
AU - Kleiner, Ron
AU - Vaskovich-Koubi, Daniella
AU - Reshef, Keren
AU - Dulberg, Shai
AU - Verdial, Mafalda
AU - Conniot, João
AU - Afonso, Marta B.
AU - Acúrcio, Rita C.
AU - Basto, Afonso P.
AU - Mensurado, Sofia
AU - Silva-Santos, Bruno
AU - Santos, Susana Constantino Rosa
AU - Viana, Ana S.
AU - Silva, Liana C.
AU - Rodrigues, Cecília M.P.
AU - Préat, Véronique
AU - Graça, Luís
AU - Madi, Asaf
AU - Satchi-Fainaro, Ronit
AU - Florindo, Helena F.
N1 - Publisher Copyright:
© 2024 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH.
PY - 2024/8/14
Y1 - 2024/8/14
N2 - Breast cancer is the primary cause of cancer-related death in women worldwide. Breast cancer subtypes are characterized by different gene expression patterns, which drive their prognostic factors and therapeutic options. Among them, triple-negative breast cancer (TNBC) is one of the deadliest due to its aggressiveness, high rate of early recurrence and distant metastases, and limited therapeutic options. Despite the recent approval of monoclonal antibodies targeting programmed cell death protein 1 (PD-1) or its ligand (PD-L1) for the treatment of TNBC patients with a locally recurrent unresectable or metastatic tumor expressing PD-L1, their response rate is very modest. It is reported that polymeric nanoparticle (NP)-based cancer vaccines, co-entrapping tumor-associated antigens, Toll-like receptor ligands and small interfering RNA (siRNA) targeting the expression of the immunosuppressive cytokine transforming growth factor (TGF)-β1 by dendritic cells, sensitized TNBC to the agonist immune checkpoint OX40, inhibiting tumor growth and increasing overall survival. This anti-tumor immune-mediated effect is also observed in a luminal type of mammary cancer similar to human disease. Therefore, these synergistic anticancer effects of αOX40 and the antigen-specific adaptive immunity induced by nanovaccine-mediated TGF-β silencing may guide the development of novel combination regimens able to improve the response rate to this aggressive tumor.
AB - Breast cancer is the primary cause of cancer-related death in women worldwide. Breast cancer subtypes are characterized by different gene expression patterns, which drive their prognostic factors and therapeutic options. Among them, triple-negative breast cancer (TNBC) is one of the deadliest due to its aggressiveness, high rate of early recurrence and distant metastases, and limited therapeutic options. Despite the recent approval of monoclonal antibodies targeting programmed cell death protein 1 (PD-1) or its ligand (PD-L1) for the treatment of TNBC patients with a locally recurrent unresectable or metastatic tumor expressing PD-L1, their response rate is very modest. It is reported that polymeric nanoparticle (NP)-based cancer vaccines, co-entrapping tumor-associated antigens, Toll-like receptor ligands and small interfering RNA (siRNA) targeting the expression of the immunosuppressive cytokine transforming growth factor (TGF)-β1 by dendritic cells, sensitized TNBC to the agonist immune checkpoint OX40, inhibiting tumor growth and increasing overall survival. This anti-tumor immune-mediated effect is also observed in a luminal type of mammary cancer similar to human disease. Therefore, these synergistic anticancer effects of αOX40 and the antigen-specific adaptive immunity induced by nanovaccine-mediated TGF-β silencing may guide the development of novel combination regimens able to improve the response rate to this aggressive tumor.
KW - OX40 and PD-1
KW - RNA and vaccine co-delivery
KW - luminal B mammary cancer
KW - nanotechnology
KW - triple-negative breast cancer
UR - http://www.scopus.com/inward/record.url?scp=85189096093&partnerID=8YFLogxK
U2 - 10.1002/adfm.202401749
DO - 10.1002/adfm.202401749
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AN - SCOPUS:85189096093
SN - 1616-301X
VL - 34
JO - Advanced Functional Materials
JF - Advanced Functional Materials
IS - 33
M1 - 2401749
ER -