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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.

Surgery is the standard care for patients with stage I lung cancer. Despite successful surgery, 20-30% of patients will relapse. Chemotherapy can improve patient survival; however, it is controversial if early stage cancer patients should be treated with chemotherapy since, for many cases, it will harm quality of life with little therapeutic benefit.

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.

The invention relates to novel lipid-based nanoparticles (liposomes) for use in targeted, on demand and on site drug delivery. The particles include a wall surrounding a cavity, wherein the wall is comprised of:

1. A lipid bilayer comprising 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC_8,9PC), dipalmitoylphosphatidylcholine (DPPC), and 1,2-distearoyl-sn-glycero-3-

phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000), and