The present invention provides a universal, yet adaptable, anti-tag chimeric antigen receptor (AT-CAR) system which provides T cells with the ability and specificity to recognize and kill target cells, such as tumor cells, that have been marked by tagged antibodies. As an example, αFITC-CAR-expressing T cells have been developed that specifically recognize various human cancer cells when those cells are bound by cancer-reactive FITC-labeled antibodies. The activation of αFITC-CAR-expressing T cells is shown to induce efficient target lysis, T cell proliferation, and cytokine/chemokine production. The system can be used to treating subjects having cancer.

The present invention encompasses prodrug compositions, nanoparticles comprising one or more prodrugs, and methods of use thereof.

Pharmaceutical compositions are provided for extending the serum half-life of a therapeutic agent. The composition may include a strained alkyne-labeled therapeutic agent. Also provided is a strained alkyne-carrier protein adduct including a vinyl thioether-linkage to a cysteine residue of the carrier protein. Methods of chemoselectively modifying a carrier protein are provided, that include conjugating a cysteine residue of a carrier protein with a cyclooctyne-labeled cargo agent to produce a vinyl thioether-linked conjugate. Also provided is a method of increasing the in vivo half-life of a bioactive agent including administering a strained alkyne-labeled bioactive agent to a subject.

This disclosure relates to bivalent compounds (e.g., bi-functional small molecule compounds), compositions comprising one or more of the bivalent compounds, and to methods of use the bivalent compounds for the treatment of certain disease in a subject in need thereof. The disclosure also relates to methods for identifying such bivalent compounds.

The invention provides for bifunctional molecules comprising an UchL5 binding partner and a target protein binding partner linked via a flexible linker. A bifunctional molecule according to the invention binds to UchL5 and to the target protein, thereby facilitating degradation of the target protein bound to the target protein binding partner. The invention also provides for use of a bifunctional molecule for preventing or treating disease.

The present invention provides universal immunotherapy compositions useful for targeted treatment of cancers.

The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

Water dispersible, multivalent ligand-lipid constructs that spontaneously and stably incorporate into membranes are disclosed.

The invention discloses the use of single-stranded RNA toeholds of different lengths to promote the re-association of various RNA-DNA hybrids, which results in activation of multiple split functionalities inside human cells. Previously designed RNA/DNA nanoparticles employed single-stranded DNA toeholds to initiate re-association. The use of RNA toeholds is advantageous because of the simpler design rules, the shorter toeholds, and the smaller size of the resulting nanoparticles compared to the same hybrid nanoparticles with single-stranded DNA toeholds. Moreover, the co-transcriptional assemblies result in higher yields for hybrid nanoparticles with ssRNA toeholds.

Described herein in part are silanol based therapeutic payloads comprising a silanol terminus, a divalent spacer moiety, and a drug moiety capable of effecting a target cell or tissue.