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An ultra-long-acting L-asparaginase synergizes with an immune checkpoint inhibitor in starvation-immunotherapy of metastatic solid tumors.
Zhang, Sanke; Gong, Like; Sun, Yuanzi; Zhang, Fan; Gao, Weiping.
Afiliación
  • Zhang S; Biomedical Engineering Department, Institute of Advanced Clinical Medicine, Peking University, Beijing, 100191, China; Peking University International Cancer Institute, Beijing, 100191, China; Peking University-Yunnan Baiyao International Medical Research Center, Beijing, 100191, China.
  • Gong L; Biomedical Engineering Department, Institute of Advanced Clinical Medicine, Peking University, Beijing, 100191, China; Peking University International Cancer Institute, Beijing, 100191, China; Peking University-Yunnan Baiyao International Medical Research Center, Beijing, 100191, China.
  • Sun Y; Biomedical Engineering Department, Institute of Advanced Clinical Medicine, Peking University, Beijing, 100191, China; Peking University International Cancer Institute, Beijing, 100191, China; Peking University-Yunnan Baiyao International Medical Research Center, Beijing, 100191, China.
  • Zhang F; Biomedical Engineering Department, Institute of Advanced Clinical Medicine, Peking University, Beijing, 100191, China; Peking University International Cancer Institute, Beijing, 100191, China; Peking University-Yunnan Baiyao International Medical Research Center, Beijing, 100191, China.
  • Gao W; Biomedical Engineering Department, Institute of Advanced Clinical Medicine, Peking University, Beijing, 100191, China; Peking University International Cancer Institute, Beijing, 100191, China; Peking University-Yunnan Baiyao International Medical Research Center, Beijing, 100191, China; Department o
Biomaterials ; 312: 122740, 2025 Jan.
Article en En | MEDLINE | ID: mdl-39096839
ABSTRACT
Metastasis stands as the primary contributor to mortality associated with tumors. Chemotherapy and immunotherapy are frequently utilized in the management of metastatic solid tumors. Nevertheless, these therapeutic modalities are linked to serious adverse effects and limited effectiveness in preventing metastasis. Here, we report a novel therapeutic strategy named starvation-immunotherapy, wherein an immune checkpoint inhibitor is combined with an ultra-long-acting L-asparaginase that is a fusion protein comprising L-asparaginase (ASNase) and an elastin-like polypeptide (ELP), termed ASNase-ELP. ASNase-ELP's thermosensitivity enables it to generate an in-situ depot following an intratumoral injection, yielding increased dose tolerance, improved pharmacokinetics, sustained release, optimized biodistribution, and augmented tumor retention compared to free ASNase. As a result, in murine models of oral cancer, melanoma, and cervical cancer, the antitumor efficacy of ASNase-ELP by selectively and sustainably depleting L-asparagine essential for tumor cell survival was substantially superior to that of ASNase or Cisplatin, a first-line anti-solid tumor medicine, without any observable adverse effects. Furthermore, the combination of ASNase-ELP and an immune checkpoint inhibitor was more effective than either therapy alone in impeding melanoma metastasis. Overall, the synergistic strategy of starvation-immunotherapy holds excellent promise in reshaping the therapeutic landscape of refractory metastatic tumors and offering a new alternative for next-generation oncology treatments.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asparaginasa / Inhibidores de Puntos de Control Inmunológico / Inmunoterapia Límite: Animals / Female / Humans Idioma: En Revista: Biomaterials Año: 2025 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asparaginasa / Inhibidores de Puntos de Control Inmunológico / Inmunoterapia Límite: Animals / Female / Humans Idioma: En Revista: Biomaterials Año: 2025 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos