SpCas9-expression by tumor cells can cause T cell-dependent tumor rejection in immunocompetent mice

OncoImmunology

Reham Ajina¹  Marta Catalfamo¹  Annie Zuo¹  Louis M. Weiner¹  Maha Moussa¹  Sandra A. Jablonski¹  Danielle Zamalin² 

[1] Georgetown University Medical Center;School of Nursing and Health Studies, Georgetown University;

关键词: crispr-cas9;    spcas9;    crispr;    immunity;   

DOI  :  10.1080/2162402X.2019.1577127

来源: DOAJ

【 摘 要 】

The CRISPR/Cas9 system has recently emerged as a highly efficient modality in genetic engineering and has been widely considered for various therapeutic applications. However, since the effector protein, SpCas9, has a bacterial origin, its immunogenicity must be explored in further depth. Here, we found that the intact immune system, in wild-type C57BL/6J and BALB/cL mice, stimulates specific immune response against SpCas9, resulting in the rejection of SpCas9-expressing tumors. However, these tumors effectively grew in syngeneic C57BL/6J immunodeficient, T cell-depleted and Cas9-KI mice. Therefore, these observations suggest that this tumor rejection phenotype is T cell-dependent. The immunological clearance of SpCas9-expressing tumors in the immunocompetent group illustrates the possibility of misinterpreting the impact of CRISPR/Cas9-mediated gene editing on in vivo tumor biology and survival. Thus, these findings have important implications for the use of this exciting approach in in vivo studies, as well as to manipulate cancer cell biology for therapeutic applications.

【 授权许可】

Unknown