A Novel CXCR4-Targeted Diphtheria Toxin Nanoparticle Inhibits Invasion and Metastatic Dissemination in a Head and Neck Squamous Cell Carcinoma Mouse Model
Por:
Rioja-Blanco, E, Gallardo, A, Arroyo-Solera, I, Alamo, P, Casanova, I, Unzueta, U, Serna, N, Sanchez-Garcia, L, Quer, M, Villaverde, A, Vazquez, E, Leon, X, Alba-Castellon, L, Mangues, R
Publicada:
1 abr 2022
Resumen:
Loco-regional recurrences and metastasis represent the leading causes of death in head and neck squamous cell carcinoma (HNSCC) patients, highlighting the need for novel therapies. Chemokine receptor 4 (CXCR4) has been related to loco-regional and distant recurrence and worse patient prognosis. In this regard, we developed a novel protein nanoparticle, T22-DITOX-H6, aiming to selectively deliver the diphtheria toxin cytotoxic domain to CXCR4(+) HNSCC cells. The antimetastatic effect of T22-DITOX-H6 was evaluated in vivo in an orthotopic mouse model. IVIS imaging system was utilized to assess the metastatic dissemination in the mouse model. Immunohistochemistry and histopathological analyses were used to study the CXCR4 expression in the cancer cells, to evaluate the effect of the nanotoxin treatment, and its potential off-target toxicity. In this study, we report that CXCR4(+) cancer cells were present in the invasive tumor front in an orthotopic mouse model. Upon repeated T22-DITOX-H6 administration, the number of CXCR4(+) cancer cells was significantly reduced. Similarly, nanotoxin treatment effectively blocked regional and distant metastatic dissemination in the absence of systemic toxicity in the metastatic HNSCC mouse model. The repeated administration of T22-DITOX-H6 clearly abrogates tumor invasiveness and metastatic dissemination without inducing any off-target toxicity. Thus, T22-DITOX-H6 holds great promise for the treatment of CXCR4(+) HNSCC patients presenting worse prognosis.
Filiaciones:
Rioja-Blanco, E:
Inst Invest Biomed St Pau IIB St Pau, St Quinti 77, Barcelona 08041, Spain
Inst Recerca Leucemia Josep Carreras, Barcelona 08025, Spain
Gallardo, A:
Inst Invest Biomed St Pau IIB St Pau, St Quinti 77, Barcelona 08041, Spain
Hosp Santa Creu & Sant Pau, Dept Pathol, St Quinti 89, Barcelona 08041, Spain
Arroyo-Solera, I:
Inst Invest Biomed St Pau IIB St Pau, St Quinti 77, Barcelona 08041, Spain
Inst Recerca Leucemia Josep Carreras, Barcelona 08025, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Monforte Lemos 3-5, Madrid 28029, Spain
Alamo, P:
Inst Invest Biomed St Pau IIB St Pau, St Quinti 77, Barcelona 08041, Spain
Inst Recerca Leucemia Josep Carreras, Barcelona 08025, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Monforte Lemos 3-5, Madrid 28029, Spain
Casanova, I:
Inst Invest Biomed St Pau IIB St Pau, St Quinti 77, Barcelona 08041, Spain
Inst Recerca Leucemia Josep Carreras, Barcelona 08025, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Monforte Lemos 3-5, Madrid 28029, Spain
Unzueta, U:
Inst Invest Biomed St Pau IIB St Pau, St Quinti 77, Barcelona 08041, Spain
Inst Recerca Leucemia Josep Carreras, Barcelona 08025, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Monforte Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Serna, N:
CIBER Bioingn Biomat & Nanomed CIBER BBN, Monforte Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Sanchez-Garcia, L:
CIBER Bioingn Biomat & Nanomed CIBER BBN, Monforte Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Quer, M:
CIBER Bioingn Biomat & Nanomed CIBER BBN, Monforte Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Otorhinolaryngol, Hosp Santa Creu & St Pau, St Quinti 89, Barcelona 08041, Spain
Villaverde, A:
CIBER Bioingn Biomat & Nanomed CIBER BBN, Monforte Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Vazquez, E:
CIBER Bioingn Biomat & Nanomed CIBER BBN, Monforte Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Bellaterra 08193, Spain
Leon, X:
CIBER Bioingn Biomat & Nanomed CIBER BBN, Monforte Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Otorhinolaryngol, Hosp Santa Creu & St Pau, St Quinti 89, Barcelona 08041, Spain
Alba-Castellon, L:
Inst Invest Biomed St Pau IIB St Pau, St Quinti 77, Barcelona 08041, Spain
Inst Recerca Leucemia Josep Carreras, Barcelona 08025, Spain
Mangues, R:
Inst Invest Biomed St Pau IIB St Pau, St Quinti 77, Barcelona 08041, Spain
Inst Recerca Leucemia Josep Carreras, Barcelona 08025, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, Monforte Lemos 3-5, Madrid 28029, Spain
gold, Green Published, All Open Access, Gold, Green
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