The present invention provides multispecific antibodies that bind to EGFR and CD28 (EGFRxCD28) as well as anti-EGFR antibodies. Such antibodies may be combined with a further therapeutic agent such as an anti-PD1 antibody. Methods for treating cancers (e.g., EGFR-expressing cancer) by administering the antibodies (e.g., and combinations thereof with anti-PD1) are also provided. The EGFRxCD28 antibodies of the present invention embody a tumor-targeted immunotherapeutic modality combined with PD-1 inhibition. These bispecific antibodies bind a tumor-specific antigen (TSA) (EGFR) with one arm and the co-stimulatory receptor, CD28, on T-cells with the other arm. Combination therapy with PD-1 inhibitors specifically potentiated intra-tumoral T cell activation, promoting an effector memory-like T cell phenotype without systemic cytokine secretion in a variety of syngeneic and human tumor xenograft models. Combining this class of CD28-co-stimulatory bispecific antibodies with the clinically validated anti-PD-1 treatment provides a well-tolerated antibody therapy with markedly enhanced anti-tumor efficacy.

A significant interferon (IFN) response is induced following treatment of CHO cells with exogenously-added type I IFN or poly I:C. Treatment of the CHO cells with poly I:C prior to infection limited the cytopathic effect from Vesicular stomatitis virus (VSV), Encephalomyocarditis vims (EMCV), and Reovirus-3 vims (Reo) in a STAT1-dependent manner By knocking out two upstream repressors of STAT1: Gfi1 and Trim 24, the engineered CHO cells exhibited increased resistance to virus contaminations. Thus, omics-guided engineering of mammalian cell culture can be deployed to increase safety in biotherapeutic protein production.

The invention provides inducible promoter systems and their components incorporating components of a tetracycline operon. By coordinating expression of different transcriptional units in these systems as a result of selection of promoters and/or linking the units into the same DNA molecule, these systems can achieve higher levels of expression of coding segments of interest, increased differential levels of expression between on- and off-states, and/or greater responsiveness to inducing agents than conventional systems.

Disclosed are a method and culture medium for performing an in vivo treatment on ovaries of mammals including humans or performing in vitro culturing on ex vivo ovaries or ovarian tissue by means of using 4-vinylcyclohexene diepoxide. The method or culture medium provided facilitates the retention and enhancement of the developmental and reproductive potential of mammalian ovaries or ovarian tissue, and is particularly capable of promoting follicle maturation and increasing the number of ovulations.

The present invention relates to inhibitors of protein fucosylation. More specifically, the present invention relates to carbacyclic compounds of Formula (I) useful as inhibitors of protein fucosylation, or for treating a cancer, an autoimmune disease, an infectious disease, an inflammatory disease, or sickle cell disease.

##STR00001##

Provided is a method of culturing stem cells, comprising a step of culturing stem cells in an atmospheric environment comprising an additional pressure applied in addition to an atmospheric pressure, wherein the additional pressure may be about 60-140 mmHg. Also provided are stem cells obtained according to the method of culturing.

Abstract: The present invention belongs to the field of biotechnology, and specifically relates to recombinant gene expression. The invention concerns a method of recombinant gene expression from a Chinese Hamster Ovary (CHO) cell, by using super-enhancer sequences for increased gene expression. Thus, the invention provides a method for producing an engineered CHO cell by introducing into the cell an exogenous nucleic acid molecule into or within 500 kb upstream or downstream of a super-enhancer as expression-enhancing sequence. The invention further provides an engineered CHO cell produced by the method. The invention further provides a method of producing a recombinant polypeptide. The invention is further directed to the use of a super-enhancer for transgene expression.

The disclosure relates to methods for handling and supplementation of cell culture medium to improve process performance in eukaryotic recombinant expression systems.

An implant for ovarian decline is provided. The implant includes at least an engineered ovarian support cell an extracellular matrix substrate, and a delivery apparatus. In some embodiments, the at least an engineered ovarian support cell includes an engineered granulosa cell. In other embodiments, the at least an engineered ovarian support cell includes an engineered lutein cell. In other embodiments, the at least an engineered ovarian support cell includes an engineered theca cell.

In accordance with the present invention, CHO cells expressing a recombinant polypeptide of interest are grown in media where the amino acids, vitamins, phosphate, lipids and/or antioxidant optimization is utilized to manipulate and/or control the protein quality attributes of the polypeptides. Polypeptides expressed in accordance with the present invention may be advantageously used in the preparation of pharmaceutical compositions.