摘要：Introducing chimeric antigen receptor into immune cells against malignancies has contributed to a revolutionary innovation in cancer immunotherapy. As an important type of adaptive immune cells, T cells first caught researchers' attention and became great success in chimeric antigen receptor-based immunotherapy. However, engineered T cells seem to hit their bottleneck when resistance of cancerous cells, less encouraging responses in solid tumors and unwanted toxicities to the host remain to be ***, innate immune cells get to join the race. Representatives such as natural killer cells, natural killer T cells, γδT cells and macrophages also prove to be well redirected with chimeric antigen receptors. Compared to chimeric antigen receptor engineered T cells, these engineered innate immune cells may possess multiple targeting and killing mechanisms, have the potential to crack the barrier of solid tumors and have less side effects in the host. Besides, possible universal access to cell resources and improvements in expansion and transduction techniques make these cells promising candidates with huge potential in translational medicine. Therefore, innate immune cells claim a brand-new dimension and are likely to supplement T cells greatly in the field of chimeric antigen receptor-based immunotherapy.

摘要：Colorectal cancer(CRC)remains one of the major causes of death worldwide,despite steady improvement in early detection and overall survival over the past *** treatment paradigms,with chemotherapy and biologics,appear to have reached their maximum ***,especially with checkpoint inhibitors,has shown considerable clinical benefit in various cancers,including mismatch-repair-deficient *** has led to the planning and initiation of several clinical trials evaluating novel immunotherapy agents—as single agents,combinations and in conjunction with chemotherapy—in patients with *** article reviews biological and preclinical data for checkpoint inhibitors and discusses various immunotherapy trials in CRC,as well as current efforts in CRC immunotherapy.

摘要：Glioblastoma (GBM) is the most common primary brain malignancy in adults and has a poor prognosis despite standard of care treatment. The mainstay of GBM treatment has relied on maximum surgical resection and chemotherapy and radiation. Cancer immunotherapy has made great strides since the advent of anti-PD-1, anti-CTLA-4, and other immune checkpoint inhibitors. With the advancement of novel therapeutics, more clinical trials for patients have opened as well. An important future direction of clinical trials is the ability to identify appropriate patients to optimize treatment response and minimize toxicities. This review describes considerations in designing future GBM clinical trials in not only immunotherapy but also with other promising treatments. We will discuss factors, such as pseudoprogression, genetic and circulating biomarkers, and the commensal microbiome of patients in the setting of clinical trial design.

摘要：The stimulator of interferon genes(STING)shows promising clinical activity in infectious diseases and ***,the lack of targeting capability and intracellular stability of STING agonists severely limits the therapeutic ***,drug delivery systems(DDSs)overcome these delivery barriers of STING agonists via passive or active cell targeting,prolonged blood circulation and drug release,and lysosome escape,*** this review,we will describe in detail how existing DDSs are designed to overcome delivery barriers and activate the STING pathway,and the current biomedical applications of STING-activating DDSs in the treatments of infectious diseases and ***,the prospects and challenges of DDSs in STING activation are discussed.

摘要：T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for immunotherapeutic targeting of tumor cells in a non-HLA restricted manner. In this study we transduced T cells with a CD19-CAR construct containing a truncated CD34 gene (tCD34) marker and used these to target the B cell antigen CD19 on the surface of a Hodgkin’s lymphoma (HL) cell line (L591) both in vitro and in vivo. Levels of tCD34 expression in transduced peripheral blood mononuclear cells (PBMCs) ranged from 6% - 20% and this was increased to 82% after selection for transduced tCD34+ cells. In vitro cytotoxicity testing on a CD19+ HL cell line (L591) showed specific cell lysis initiated by the CD19-CAR transduced PBMCs. Importantly, CD19-CAR T cells prevented the growth of L591 HL tumor cells when co-injected subcutaneously (sc) in 6/6 severe combined immunodeficient (SCID) mice. There was no evidence of anti-tumor activity when CD19-CAR T cells were infused intravenously (iv) at the same time as L591 HL tumor cells were injected sc. However, 3/6 SCID mice showed tumor rejection within 83 days after iv infusion of CD19-CAR T cells 3 - 9 days after establishment of L591 HL tumors, while all control animals succumbed to tumors within 60 days. Interestingly, immuno-histochemical analysis of L591 HL tumors demonstrated that CD19-CAR T cells were detected not earlier than 11 days after infusion within the tumor mass. These results suggest that CD19 is a potentially attractive target for the immunotherapy of HL.