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RESEARCH PRODUCT
Local delivery of mRNA-encoded cytokines promotes antitumor immunity and tumor eradication across multiple preclinical tumor models
Kuldeep SinghNatalia MalkovaChristian HotzJan DiekmannGang ZhengSonja WitzelMichelle CallahanQunyan YuHui QuJoanne LagerDinesh S. BangariSerena MasciariGary J. NabelJulia SchlerethYu-an ZhangAndreas KuhnDmitri WiederschainKarl HsuUgur SahinMarie BernardoMustafa DikenMikhail LevitFriederike GiesekeAndy HebertBodo TillmannAbderaouf SelmiJack PollardSue RyanChristian GrunwitzFangxian SunKatalin KarikóLena WickeHui CaoWilliam WeberTimothy R. WagenaarSebastian KreiterTatiana Tolstykhsubject
Messenger RNAAntitumor immunitybusiness.industrymedicine.medical_treatmentRNANeoplasms therapyGeneral MedicineImmunotherapyArticleImmune systemNeoplasmsCancer researchSystemic administrationCytokinesHumansMedicineRNA MessengerbusinessGenedescription
Local immunotherapy ideally stimulates immune responses against tumors while avoiding toxicities associated with systemic administration. Current strategies for tumor-targeted, gene-based delivery, however, are limited by adverse effects such as off-targeting or antivector immunity. We investigated the intratumoral administration of saline-formulated messenger (m)RNA encoding four cytokines that were identified as mediators of tumor regression across different tumor models: interleukin-12 (IL-12) single chain, interferon-α (IFN-α), granulocyte-macrophage colony-stimulating factor, and IL-15 sushi. Effective antitumor activity of these cytokines relied on multiple immune cell populations and was accompanied by intratumoral IFN-γ induction, systemic antigen-specific T cell expansion, increased granzyme B
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-09-13 | Science Translational Medicine |