Disclosed herein are methods of producing chimeric antigen receptor (CAR) T cells using substrates, such as artificial antigen presenting cells, containing on a surface a a heparin binding domain (HBD), anti-CD3 single chain antibodies, anti-CD28 single chain antibodies (scFv), and optionally anti-41BBL antibodies. Anti-CD3 and Anti-CD28 scFvs bind and activate expanding T cells ex vivo, while the Heparin Binding Domain binds the viral vector, thereby bringing the T cells into close proximity with virus for effective gene transfer. This is a less costly, renewable, modifiable, and efficacious alternative to coated beads and RetroNectin® for gene transfer.

Disclosed herein are methods of producing chimeric antigen receptor (CAR) T cells using substrates, such as artificial antigen presenting cells, containing on a surface a a heparin binding domain (HBD), anti-CD3 single chain antibodies, anti-CD28 single chain antibodies (scFv), and optionally anti-41BBL antibodies. Anti-CD3 and Anti-CD28 scFvs bind and activate expanding T cells ex vivo, while the Heparin Binding Domain binds the viral vector, thereby bringing the T cells into close proximity with virus for effective gene transfer. This is a less costly, renewable, modifiable, and efficacious alternative to coated beads and RetroNectin® for gene transfer.

The present invention relates to a cleavable linker platform. In particular, the invention relates to construction of an enzyme cleavable linker platform conjugated to a drug or a diagnostically relevant compound, a biomolecule, and an enzyme cleavable group, for which cleavage of the enzyme cleavable group leads to release of the drug or diagnostically relevant compound.

The present invention relates to a cleavable linker platform. In particular, the invention relates to construction of an enzyme cleavable linker platform conjugated to a drug or a diagnostically relevant compound, a biomolecule, and an enzyme cleavable group, for which cleavage of the enzyme cleavable group leads to release of the drug or diagnostically relevant compound.

A bio-related substance bonded to a branched and degradable polyethylene glycol derivative that is degraded in the cells represented by the following formula (A):

##STR00001##

wherein each symbol is as defined in the present specification, is provided by the present invention.

PSMA targeted conjugate compounds, pharmaceutical compositions comprising these compounds, methods for treating and detecting cancers in a subject, methods for identifying cancer cells in a sample are described herein.

The disclosure relates to methods for treating cancer. More particularly, the disclosure relates to use of chimeric non-natural synthetic proteins, in combination with non-tyrosine targeting kinase inhibitors (NTKIs), in treating cancer and preventing intrinsic and/or acquired resistance to NTKIs.

The disclosure relates to methods for treating cancer. More particularly, the disclosure relates to use of chimeric non-natural synthetic proteins, in combination with non-tyrosine targeting kinase inhibitors (NTKIs), in treating cancer and preventing intrinsic and/or acquired resistance to NTKIs.

A multi-arm, degradable polyethylene glycol derivative with a high molecular weight that does not cause vacuolation of cells is provided. A degradable polyethylene glycol derivative represented by the following formula (1):

##STR00001##

wherein n1 and n2 are each independently 45-950, W.sup.1 and W.sup.2 are each independently an oligopeptide of 2-47 residues, a1 and a2 are each independently 1-8, Q is a hydrocarbon chain having 2-12 carbon atoms and optionally containing an oxygen atom and/or a nitrogen atom, X.sup.1 and X.sup.2 are each independently a functional group capable of reacting with a bio-related substance, and L.sup.1, L.sup.2, L.sup.3, L.sup.4, L.sup.5 and L.sup.6 are each independently a divalent spacer.

The present disclosure provides scaffolds and antibody-drug conjugates (ADCs) comprising a stimulator of interferon genes (STING). The present disclosure also provides uses of the ADCs in treatment, e.g., treatment of cancer.