PRECLINICAL MOUSE MODELS IN ADOPTIVE CELL THERAPIES OF CANCER
DOI:
https://doi.org/10.26873/SVR-1513-2022Keywords:
mouse model, xenograft, syngeneic, transgenic, humanized, CAR-T, adoptive cell therapyAbstract
Engineered T cell-based therapies are an advanced approach for cancer immunotherapy using genetically modi- fied T cells. To date, CD19 and BCMA targeting Chimeric Antigen Receptor (CAR) T cells have been approved for the treatment of certain hematologic malignancies. The success of CAR-T cells is offset by limited efficacy, particularly in solid tumors, and safety risks. Preclinical in vivo research, which is highly dependent on reliable mouse models, has been a cornerstone of the suc- cess story of adoptive cell therapies and continues to provide invaluable information for the development of the next generation of cellular immunotherapies. In this review we describe four of the most common preclinical mouse models: xenograft models, syngeneic models, immunocompetent transgenic models and humanized mouse models. All of these have advantages and disadvantages and no mouse model can fully recapitulate the human situation because of inherent differences and treatment complexity. Reports suggest that using a combination of mouse models in preclinical in vivo research prior to translating the treat- ment to humans in clinical trials can help incrementally improve the quality, safety, and efficacy of the treatment and provide more comprehensive information than a single model.
PREDKLINIČNI MIŠJI MODELI PRI ADOPTIVNIH CELIČNIH TERAPIJAH RAKA
Izvleček: Napredne terapije na osnovi biotehnološko spremenjenih limfocitov T predstavljajo moderen pristop k imunoter- apiji raka z uporabo genetsko spremenjenih limfocitov T. Do danes sta bili za zdravljenje hematoloških malignosti odobreni terapiji s himernimi antigenskimi receptorji usmerjenimi proti antigenoma CD19 in BCMA. Uspeh zdravljenja s celicami CAR-T pa ovirajo omejena učinkovitost, še posebej pri solidnih tumorjih in varnostna tveganja. Predklinične raziskave in vivo, ki so močno odvisne od zanesljivih mišjih modelov, so bile kritični dejavnik zgodbe o uspehu adoptivnih celičnih terapij in še vedno zagotavljajo neprecenljive podatke za razvoj naslednje generacije celičnih imunoterapij. V preglednem članku povzemamo štiri najpogostejše predklinične mišje modele: ksenografte, singenetske modele, imunokompetentne transgenske modele in humanizirane mišje modele. Vsi opisani modeli imajo svoje prednosti in slabosti in noben mišji model ne more do popol- nosti preslikati situacije v človeškem pacientu zaradi medvrstnih razlik ter izjemne zapletenosti zdravljenja. Podatki iz literature kažejo na to, da lahko uporaba kombinacije mišjih modelov v predkliničnih in vivo raziskavah pred translacijo zdravljenja na ljudi v kliničnih poskusih pripomore k postopnemu izboljšanju kakovosti, varnosti in učinkovitosti zdravljenja in zagotovi bolj celostni nabor podatkov kot en sam model.
Ključne besede: mišji model; ksenograft; singenetski; transgenski; humanizirani; CAR-T; adoptivna celična terapija
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