Neoantigens:promising targets for cancer therapy

Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies,including cancer vaccines,adoptive cell therapy and antibody-based therapies,especially for solid tumors.Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations,such as genomic mutation,dysregulated RNA splicing,disordered post-translational modification,and integrated viral open reading frames.Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance.The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies.Compared to tumor-associated antigens,the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies,and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses.The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies.This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens.We also explore their current status,inherent challenges,and clinical translation potential.

Prenatal Diagnosis of Dystrophinopathy and Cytogenetic Analysis in 303 Chinese Families

Objective:This study was to supply information of the Duchenne muscular dystrophy(DMD)mutational spectrum in 303 Chinese families and further offer 5-year clinical experience of DMD/Becker muscular dystrophy genetic counseling and prenatal diagnosis.Methods:In this retrospective cohort study,three hundred and five pregnancies in 303 pregnant women who has a birth history of DMD/Becker muscular dystrophy patients underwent prenatal diagnosis using multiplex ligation-dependent probe amplification followed by Sanger sequencing between January 2014 and December 2018 at Peking Union Medical College Hospital.The mean age of pregnant women was(33.0±4.1)years old.Karyotype analysis was performed to exclude fetal abnormal karyotype.Results:The detection rate of DMD gene mutation in 303 probands was(296/303)97.7%with seven families having a negative genetic diagnosis.The mutational spectrum comprised of large arrangements in 288/303(95.0%)and small mutations in 8/303(2.6%).Carrier testing was performed among 204 pregnant women among whom,108 mothers had the same mutation as family proband.Of the 305 pregnancies underwent prenatal diagnosis,55 of 173 male fetuses were affected.We also performed karyotype analysis and found three abnormal karyotypes of trisomy 21.We even found a fetus with DMD gene mutation and trisomy 21 in a same fetus by further analysis.We also identified two times of germline mosaicism.Conclusion:This study demonstrated the distribution and mutation profile of 303 probands and 305 fetuses.Furthermore,considering the possbility of maternl germilne mosaicism,prenatal diagnosis should be suggested to mothers with a proband whether they carry the causative mutation in their blood or not.