ABSTRACT
Recent progress in chimeric antigen receptor-modified T-cell (CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines. One set of CAR-T cells contained SM3 single chain variable fragment (scFv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin (IL) 12 (named SM3-CAR). The other CAR-T cell line carried the SM3 scFv sequence modified to improve its binding to MUC1 antigen (named pSM3-CAR) but did not co-express IL-12. When those two types of CAR-T cells were injected intratumorally into two independent metastatic lesions of the same MUC1(+) seminal vesicle cancer patient as part of an interventional treatment strategy, the initial results indicated no side-effects of the MUC1 targeting CAR-T cell approach, and patient serum cytokines responses were positive. Further evaluation showed that pSM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors.
Subject(s)
Genital Neoplasms, Male/therapy , Immunotherapy, Adoptive/methods , Recombinant Fusion Proteins/metabolism , T-Lymphocytes/transplantation , Cell Line, Tumor , Cell Survival/immunology , Cells, Cultured , Coculture Techniques , Genital Neoplasms, Male/genetics , Genital Neoplasms, Male/immunology , HEK293 Cells , Humans , MCF-7 Cells , Male , Mucin-1/genetics , Mucin-1/immunology , Mucin-1/metabolism , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/metabolism , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Seminal Vesicles/pathology , Single-Chain Antibodies/genetics , Single-Chain Antibodies/immunology , Single-Chain Antibodies/metabolism , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Treatment OutcomeABSTRACT
Historical records can provide important evidence of changes in distributions of wildlife species. Here we discuss the distribution of the tiger (Panthera tigris Linnaeus, 1758) over the past 2000 years in China based on 2635 historical records. We also compare tiger distributions outlined in these records with ecosystem type maps. Throughout this time period, tigers maintained a broad distribution across 7 biomes (from forests to deserts). However, in recent decades the range has been significantly condensed. Today, only 2 populations remain, neither of which is independently viable. Tigers have completely disappeared from the temperate broadleaf and mixed forests of central China, a region that was traditionally their most important biome in China. The continued presence of wild tigers in China is highly dependent on significant conservation measures.
