Clinically translatable cytokine delivery platform for eradication of intraperitoneal tumors.
Sci Adv
; 8(9): eabm1032, 2022 03 04.
Article
em En
| MEDLINE
| ID: mdl-35235346
ABSTRACT
Proinflammatory cytokines have been approved by the Food and Drug Administration for the treatment of metastatic melanoma and renal carcinoma. However, effective cytokine therapy requires high-dose infusions that can result in antidrug antibodies and/or systemic side effects that limit long-term benefits. To overcome these limitations, we developed a clinically translatable cytokine delivery platform composed of polymer-encapsulated human ARPE-19 (RPE) cells that produce natural cytokines. Tumor-adjacent administration of these capsules demonstrated predictable dose modulation with spatial and temporal control and enabled peritoneal cancer immunotherapy without systemic toxicities. Interleukin-2 (IL2)-producing cytokine factory treatment eradicated peritoneal tumors in ovarian and colorectal mouse models. Furthermore, computational pharmacokinetic modeling predicts clinical translatability to humans. Notably, this platform elicited T cell responses in NHPs, consistent with reported biomarkers of treatment efficacy without toxicity. Combined, our findings demonstrate the safety and efficacy of IL2 cytokine factories in preclinical animal models and provide rationale for future clinical testing in humans.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucina-2
/
Melanoma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos