Hepatocellular carcinoma(HCC)arises on the background of chronic liver disease.Despite the development of effective anti-viral therapeutics HCC is continuing to rise,in part driven by the epidemic of non-alcoholic fat...Hepatocellular carcinoma(HCC)arises on the background of chronic liver disease.Despite the development of effective anti-viral therapeutics HCC is continuing to rise,in part driven by the epidemic of non-alcoholic fatty liver disease.Many patients present with advanced disease out with the criteria for transplant,resection or even locoregional therapy.Currently available therapeutics for HCC are effective in a small minority of individuals.However,there has been a major global interest in immunotherapies for cancer and although HCC has lagged behind other cancers,great opportunities now exist for treating HCC with newer and more sophisticated agents.Whilst checkpoint inhibitors are at the forefront of this revolution,other therapeutics such as inhibitory cytokine blockade,oncolytic viruses,adoptive cellular therapies and vaccines are emerging.Broadly these may be categorized as either boosting existing immune response or stimulating de novo immune response.Although some of these agents have shown promising results as monotherapy in early phase trials it may well be that their future role will be as combination therapy,either in combination with one another or in combination with treatment modalities such as locoregional therapy.Together these agents are likely to generate new and exciting opportunities for treating HCC,which are summarized in this review.展开更多
Chimeric antigen receptor （CAR） is a recombinant immunoreceptor combining an antibody-derived target- ing fragment with signaling domains capable of acti- vating cells, which endows T cells with the ability to recog...Chimeric antigen receptor （CAR） is a recombinant immunoreceptor combining an antibody-derived target- ing fragment with signaling domains capable of acti- vating cells, which endows T cells with the ability to recognize tumor-associated surface antigens indepen- dent of the expression of major histocompatibiiity complex （MHC） molecules. Recent early-phase clinical trials of CAR-modified T （CAR-T） cells for relapsed or refractory B cell malignancies have demonstrated promising results （that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia （B-ALL））. Given this suc- cess, broadening the clinical experience of CAR-T cell therapy beyond hematological malignancies has been actively investigated. Here we discuss the basic design of CAR and review the clinical results from the studies of CAR-T cells in B cell leukemia and lymphoma, and several solid tumors. We additionally discuss the major challenges in the further development and strategies for increasing anti-tumor activity and safety, as well as for successful commercial translation.展开更多
文摘Hepatocellular carcinoma(HCC)arises on the background of chronic liver disease.Despite the development of effective anti-viral therapeutics HCC is continuing to rise,in part driven by the epidemic of non-alcoholic fatty liver disease.Many patients present with advanced disease out with the criteria for transplant,resection or even locoregional therapy.Currently available therapeutics for HCC are effective in a small minority of individuals.However,there has been a major global interest in immunotherapies for cancer and although HCC has lagged behind other cancers,great opportunities now exist for treating HCC with newer and more sophisticated agents.Whilst checkpoint inhibitors are at the forefront of this revolution,other therapeutics such as inhibitory cytokine blockade,oncolytic viruses,adoptive cellular therapies and vaccines are emerging.Broadly these may be categorized as either boosting existing immune response or stimulating de novo immune response.Although some of these agents have shown promising results as monotherapy in early phase trials it may well be that their future role will be as combination therapy,either in combination with one another or in combination with treatment modalities such as locoregional therapy.Together these agents are likely to generate new and exciting opportunities for treating HCC,which are summarized in this review.
文摘Chimeric antigen receptor （CAR） is a recombinant immunoreceptor combining an antibody-derived target- ing fragment with signaling domains capable of acti- vating cells, which endows T cells with the ability to recognize tumor-associated surface antigens indepen- dent of the expression of major histocompatibiiity complex （MHC） molecules. Recent early-phase clinical trials of CAR-modified T （CAR-T） cells for relapsed or refractory B cell malignancies have demonstrated promising results （that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia （B-ALL））. Given this suc- cess, broadening the clinical experience of CAR-T cell therapy beyond hematological malignancies has been actively investigated. Here we discuss the basic design of CAR and review the clinical results from the studies of CAR-T cells in B cell leukemia and lymphoma, and several solid tumors. We additionally discuss the major challenges in the further development and strategies for increasing anti-tumor activity and safety, as well as for successful commercial translation.
