Chimeric antigen receptor T (CAR-T) cells have shown promising efficacy in treatment of hematological malignancies, but its applications in solid tumors need further exploration. In this study, we investigated CAR-T therapy targeting carcino-embryonic antigen (CEA)-positive colorectal cancer (CRC) patients with metastases to evaluate its safety and efficacy. Five escalating dose levels (DLs) (1 × 105 to 1 × 108/CAR+/kg cells) of CAR-T were applied in 10 CRC patients. Our data showed that severe adverse events related to CAR-T therapy were not observed. Of the 10 patients, 7 patients who experienced progressive disease (PD) in previous treatments had stable disease after CAR-T therapy. Two patients remained with stable disease for more than 30 weeks, and two patients showed tumor shrinkage by positron emission tomography (PET)/computed tomography (CT) and MRI analysis, respectively. Decline of serum CEA level was apparent in most patients even in long-term observation. Furthermore, we observed persistence of CAR-T cells in peripheral blood of patients receiving high doses of CAR-T therapy. Importantly, we observed CAR-T cell proliferation especially in patients after a second CAR-T therapy. Taken together, we demonstrated that CEA CAR-T cell therapy was well tolerated in CEA+ CRC patients even in high doses, and some efficacy was observed in most of the treated patients.

Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer

Bispecific antibodies (BsAbs) are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. The clinical therapeutic effects of BsAbs are superior to those of monoclonal antibodies (MoAbs), with broad applications for tumor immunotherapy as well as for the treatment of other diseases. Recently, with progress in antibody or protein engineering and recombinant DNA technology, various platforms for generating different types of BsAbs based on novel strategies, for various uses, have been established. More than 30 mature commercial technology platforms have been used to create and develop BsAbs based on the heterologous recombination of heavy chains and matching of light chains. The detailed mechanisms of clinical/therapeutic action have been demonstrated with these different types of BsAbs. Three kinds of BsAbs have received market approval, and more than 110 types of BsAbs are at various stages of clinical trials. In this paper, we elaborate on the classic platforms, mechanisms, and applications of BsAbs. We hope that this review can stimulate new ideas for the development of BsAbs and improve current clinical strategies.

Hepatocellular carcinoma (HCC) is a highly aggressive liver tumor containing cancer stem cells (CSCs) that participate in tumor propagation, resistance to conventional therapy, and promotion of tumor recurrence, causing poor patient outcomes. The protein SRY (sex determining region Y)‐box 9 (Sox9) is a transcription factor expressed in some solid tumors, including HCC. However, the molecular mechanisms underlying Sox9 function in liver CSCs remain unclear. Here, we show that Sox9 is highly expressed in liver CSCs and that high levels of Sox9 predict a decreased probability of survival in HCC patients. We demonstrate that Sox9 is required for maintaining proliferation, self‐renewal, and tumorigenicity in liver CSCs. Overexpression of exogenous Sox9 in liver non‐CSCs restored self‐renewal capacity. Additionally, a reduction in the asymmetrical cell division of spheroid‐cultured liver CSCs was observed when compared with differentiated cancer cells or liver CSCs with inhibited Notch signaling. Furthermore, we demonstrate that Sox9 is responsible for the asymmetrical‐to‐symmetrical cell division switch in liver CSCs. Sox9 also negatively regulates Numb expression, contributing to a feedback circuit that maintains Notch activity and directs symmetrical cell division. Clinical analyses revealed that the Sox9HighNumbLow profile is associated with poor prognosis in human HCC patients. Conclusion: We demonstrate that Sox9 plays a critical role in self‐renewal and tumor propagation of liver CSCs and identify the molecular mechanisms regulated by Sox9 that link tumor initiation and cell division. (Hepatology 2016;64:117–129)

Persistent human papillomavirus (HPV) infection is recognized as the main cause of cervical cancer and other malignant cancers. Although early detection and treatment can be achieved by effective HPV screening methods and surgical procedures, the disease load has not been adequately mitigated yet, especially in the underdeveloped areas. Vaccine, being regarded as a more effective solution, is expected to prevent virus infection and the consequent diseases in the phases of both prevention and treatment. Currently, there are three licensed prophylactic vaccines for L1-VLPs, namely bivalent, quadrivalent and nonavalent vaccine. About 90% of HPV infections have been effectively prevented with the implementation of vaccines worldwide. However, no significant therapeutic effect has been observed on the already existed infections and lesions. Therapeutic vaccine designed for oncoprotein E6/E7 activates cellular immunity rather than focuses on neutralizing antibodies, which is considered as an ideal immune method to eliminate infection. In this review, we elaborate on the classification, mechanism, and clinical effects of HPV vaccines for disease prevention and treatment, in order to make improvements to the current situation of HPV vaccines by provoking new ideas.