Provided herein are methods for simultaneously determining the functional status of multiple signaling pathways in a diseased cell sample obtained from a subject to thereby select for therapeutic use in the subject a targeted therapeutic agent that affects the signaling pathway with the highest level of aberrant activity in the subject's cells. Also provided are methods for determining whether a signaling pathway is ultrasensitive in a diseased cell sample from a subject, also allowing for selection of an effective targeted therapeutic agent for therapeutic use in the subject. Methods of administering a selected targeted therapeutic agent to the subject are also provided.

The present invention relates to efficient methods for providing antigen-specific lymphoid cells. These lymphoid cells may be used to provide antigen specific T cell receptors having a defined MHC restriction and to identify immunologically relevant T cell epitopes. Furthermore, the present invention relates to antigen-specific T cell receptors and T cell epitopes and their use in immunotherapy.

Described herein are methods for assessing cytotoxicity of an agent. The methods include providing a target cell that has been engineered to express intracellularly a reporter that is not expressed endogenously by the target cell, exposing the target cell to an agent capable of modulating cytotoxicity and assaying the activity of the reporter, wherein a change in reporter activity relative to a reference value is indicative of the agent being able to modulate cytotoxicity of the target cell.

Aspects of the application relate to methods and systems for evaluating treatment response by measuring treatment-induced changes at the single cell level. The disclosure provides methods for isolating single cells that are primary cancer cells, including primary cancer cells from solid tumors, and detecting in minutes to hours from their removal from the body the response of such cells to anti-cancer agents such as radiation, small molecules, biologies, DNA damaging agents and the like.

The invention relates to cell death of cancer cells, and in particular to biomarkers that may be used to identify cancer cells that are sensitive to death receptor ligand (DRL)-induced cell death. The invention also extends to prognostic methods and kits for identifying cancer cells that are sensitive to DRL-induced cell death. The invention further extends to novel compositions and therapeutic methods using such compositions for treating cancer.

The present disclosure describes, in part, a Micro-organosphere immune-oncology assay and methods of making and using same. The assay quickly measures the potency of effector immune cells, such as tumor infiltrating lymphocytes, at killing a patient's tumor cells. Understanding the potency of effector immune cells is critical for adoptive T cell therapy.

A method of screening a cereblon modifying compound for treating a disease or disorder, comprising: obtaining a sample; determining a first protein level of SALL4; administering the cereblon modifying compound to the sample; determining a second protein level of SALL4; comparing the first level and the second protein level of SALL4 to determine if the cereblon modifying compound induces degradation of SALL4; and selecting the cereblon modifying compound that does not induce degradation of SALL4.

The present disclosure provides compositions comprising at least one cyclodextrin and at least one cytotoxic receptor binding small-molecule. Also disclosed are kits containing said compositions. The compositions of the present disclosure can be administered to a subject suffering from at least one type of cancer.

The present invention relates to efficient methods for providing antigen-specific lymphoid cells. These lymphoid cells may be used to provide antigen specific T cell receptors having a defined MHC restriction and to identify immunologically relevant T cell epitopes. Furthermore, the present invention relates to antigen-specific T cell receptors and T cell epitopes and their use in immunotherapy.

The invention generally relates to a microfluidic platforms or “chips” for testing and understanding cancer, and, more specifically, for understanding the factors that contribute to cancer invading tissues and causing metastases. Tumor cells are grown on microfluidic devices with other non-cancerous tissues under conditions that simulate tumor invasion. The interaction with immune cells can be tested to inhibit this activity by linking a cancer chip to a lymph chip.