Development of successful HIV vaccine immunogens continues to be a major challenge.  Although gp120 was identified as having significant potential as a vaccine immunogen, attempts to elicit broadly neutralizing antibodies using recombinant gp120 failed.  The highly flexible gp120 may present numerous conformations to the humoral immune system that are not found on the viral spike.

This invention describes a general way to trigger the release of a bioactive small molecule from a targeting antibody. The key “trigger” is a fluorescent linker that is chemically disassembled upon irradiation with light in the near-IR range (~800 nm).

Adoptive immunotherapy is a promising new approach to cancer treatment that engineers an individual''s innate and adaptive immune system to fight against specific diseases, including cancer with fewer side-effects and more specific anti-tumor activity in individual patients. T cell receptors (TCRs) and Chimeric Antigen Receptors (CARs) are proteins that recognize antigens in the context of infected or transformed cells and activate T cells to mediate an immune response to destroy abnormal cells.

CD20 is a protein expressed by wide ranges of lymphoid malignancies originating from B cells but not by indispensable normal tissues, making it an attractive target for therapies such as T-cell receptor (TCR) therapy. Current anti-CD20 therapeutics face a number of limitations. The most important limitation to current anti-CD20 therapies include cancer cells becoming resistant to the therapy.

GATA-3 is a transcription factor that is highly expressed in normal cells of the mammary luminal epithelium. GATA-3 plays a regulatory role in determining the fate of cells in the mammary gland. Disruption of GATA-3 expression leads to defects in the development of mammary cells, including an inability to differentiate properly into the correct cell type. GATA-3 function is also disrupted in various breast cancer models indicating that GATA-3 has tumor suppressive properties in normal cells.

Adoptive cell transfer (ACT) and T-cell receptor (TCR) therapies use lymphocytes that target somatic mutations expressed by tumors cells to treat cancer patients. One of the challenges of these therapies is the identification and isolation of mutation-specific cells and TCRs. While neoantigen specific cells are relatively abundant in the tumor, they are far less common in peripheral blood, a more accessible source of T cells. 

Three-dimensional (3D) cell cultures systems are important for studying cell biology because they provide in vivo-like microenvironments more physiologically relevant than two-dimensional (2D) culture systems. In 3D culture systems, cells are grown in culture matrixes and turn into spheroids and organoids later processed for downstream analysis by microscopy and histology techniques. The processing of 3D cultures for analysis by microscopy or histology is laborious and time-consuming due to incompatibility of the 3D culture vessels and the microscopy and pathology blocks.

B-cell chronic lymphocytic leukemia (B-CLL) is a cancer characterized by a progressive accumulation of functionally incompetent lymphocytes.  Despite high morbidity and mortality, the only available potential cure is allogeneic hematopoietic stem cell transplantation (alloHSCST).  However, there is less than a 50% chance of finding a matching bone marrow or blood donor for B-CLL patients.  Other clinically tested targeted therapies such as rituximab and alemtuzumab target both malignant and normal B cells, resulting in immunosuppression.

The use of tumor transcriptomics for precision oncology has made significant advances, mainly by identifying cancer driver genes or actionable mutations for treatment with targeted therapies.  However, this strategy misses out on broader genetic interactions that could reveal additional biologically testable biomarkers for therapy response prediction and inform the selection of more effective drugs for targeted treatment.

The development of precision medicine approaches for DLBCL (Diffuse Large B Cell Lymphoma) is complicated by its genetic, phenotypic and clinical heterogeneity. Current classification methods do not fully explain the observed differences in clinical outcomes to current chemotherapy and targeted therapy. Therefore, better analytical methods to classify and predict DLBCL patients’ treatment response are needed.