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The pattern or latency connectome was hypothesized to change in physiological development and disease.  For example, in amyotrophic lateral sclerosis (ALS), large diameter axons are damaged selectively – while in autism, small-diameter axons may be over-expressed. These anatomical changes are expected to alter the latency connectome or pattern of delays of information transmission between different gray matter areas involved in salient brain networks. 

Fms-like tyrosine kinase 3 (FLT3) is a cytokine receptor which belongs in the receptor tyrosine kinase class III.  FLT3 is expressed on the surface of many hematopoietic progenitor cells and plays an important role in hematopoietic stem/progenitor cell survival and proliferation.  It is often overexpressed in acute lymphoblastic leukemia (ALL) and is frequently mutated in acute myeloid leukemia (AML).  The standard therapies for ALL and AML are still suboptimal for many patients, especially pediatric.  In certain types of ALL or AML, the survival rate is less than 40 and

Heptamethine cyanines are among the most widely used near-IR fluorophores. The near-IR range (between about 650 nm and 900 nm) is very useful for imaging applications due to the absence of background autofluorescence. Despite extensive use, many of these fluorophores suffer from chemical instability. Specifically, most of the current and commonly used fluorophores undergo a phenoxy to thiol exchange reaction in the presence of primary thiols. This exchange reaction is problematic during conjugation reactions of cysteine containing macromolecules.

The clinical promise of cancer immunotherapy relies on the premise that the immune system can recognize and eliminate tumor cells identified as non-self. The success of cancer immunotherapy is limited by tumor immune evasion, preventing long-lasting tumor control. Recent evidence suggests that certain anticancer therapies can alter the biology of the surviving cell population to restore their sensitivity to T-cell-mediated lysis and help treat patients.

Ataxia telangiectasia mutated and Rad3 Related (ATR) protein kinase is essential for regulating DNA damage checkpoints during the cell cycle. ATR, is phosphorylated at threonine 1989 site (T1989) in response to DNA damage and ATR activation leads to activation of downstream substrates, signaling cascades and cell cycle arrest. ATR is a potential target for anticancer therapeutics to induce cancer cell death by inhibiting cell cycle arrest pathways in response to chemotherapeutics.

Chimeric antigen receptors (CARs) with high affinity for mesothelin that can be used as an immunotherapy to treat cancers that express mesothelin, such as pancreatic cancer, ovarian cancer, and mesothelioma. The technology includes CAR constructs with one of three different mesothelin-specific antibody portions, including either the mouse-derived SS or SS1 antibody fragments or the human HN1 antibody fragment.

The development of more targeted means of treating cancer is vital. One option for a targeted treatment is the creation of a vaccine that induces an immune response only against cancer cells. In this sense, vaccination involves the introduction of a peptide into a patient that causes the formation of antibodies or T cells that recognize the peptide. If the peptide is from a protein found selectively on/in cancer cells, those antibodies or T cells can trigger the death of those cancer cells without harming non-cancer cells. This can result in fewer side effects for the patient.

Tumors can develop unique genetic mutations which are specific to an individual patient. Some of these mutations are immunogenic; giving rise to autologous T cells which are tumor-reactive. Once isolated and sequenced, these neoantigen-specific TCRs can form the basis of effective adoptive cell therapy cancer treatment regimens; however, current methods of isolation are inefficient. Moreover, the process is technically challenging due to TCR sequence diversity and the need to correctly pair the a and b chain of each receptor.

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).

Immunotherapy is a promising method of treating cancer that leverages the immune system to promote tumor rejection. However, certain somatic mutations in cancer cells confer resistance to T cell-mediated cytolysis. To improve the effectiveness of immunotherapies for cancer, there exists a need to prospectively identify patients who are most likely to respond to such therapies.