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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.

Topoisomerase enzymes play an important role in cancer progression by controlling changes in DNA structure through catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle. Therefore, topoisomerases are important targets for cancer chemotherapy. Many topoisomerase 1 (TOP1) inhibitors such as camptothecin, rinotecan, and topotecan are widely used anti-cancer agents that work by stabilizing the TOP1-DNA cleavage complex.

Mutation of amino acid 61of the neuroblastoma rat sarcoma viral oncogene homologue (NRAS) is a known driver of oncogenesis in melanoma. Glutamine (Q) to lysine (K) mutation at this position of NRAS is prevalent in approximately 10% of all melanoma cases and associated with aggressive tumors and low patient survival. Therefore, Q61K mutated NRAS is an important candidate for targeted therapies, including cellular immunotherapy. 

Tumor cell lines are important tools for the study of cancer. However, most tumor cell lines available today do not mimic physiological tumor development, progression, and host immune responses. Autochthonous tumors include spontaneously occurring tumors and chemical, viral, or physical carcinogen-induced tumors. They are considered to model human tumors more closely than transplanted tumors. Autochthonous tumors can be generated de novo in a model organism of interest and are thought to resemble physiological human tumor conditions.

Computer and imaging technologies led to the development of digital pathology and the capture and storage of pathological specimens as digitally formatted images. The use of artificial intelligence (AI) in digital pathology, such as in three-dimensional (3D) reconstruction, requires analyses of high volumes of data. This resulted in increased demands for processing and acquisition of digital images of pathology samples. Increased usage cannot be met by the time-consuming, manual, and laborious methods currently used.

Bioluminescence imaging with luciferin-luciferase pairs is a well-established technique for tracking cells and other biological features in animal models. Bioluminescent is a chemical process which does not require an external input for excitation. Bioluminescent imaging is often limited to monitoring single processes in vivo due to the lack of distinguishable probes. Additionally, existing probes typically operate with light in the visible range, which is highly scattered and exhibits poor tissue penetration. 

CD22 is a common cell surface glycoprotein expressed in B-cells and present in B-cell lymphomas; e.g., hairy cell leukemia (HCL), non-Hodgkins lymphoma (NHL), chronic lymphoblastic leukemia (CLL), and other cancers. It is therefore a target for cancer immunotherapy. Conjugation of anti-CD22 monoclonal antibodies with toxins or drugs has shown promise in clinical trials. However, all monoclonal anti-CD22 antibodies used in clinical trials are of murine origin.

Adoptive T-cell therapy (ACT) utilizes tumor-reactive T cells to induce disease remission. While ACT has been used effectively to treat metastatic melanoma and certain epithelial cancers, most patients do not respond to treatment. Although the mechanisms underlying this variable response to therapy are not fully elucidated, the phenotype of the adoptively transferred cell is known to be a key determinant of treatment efficacy.

Polo-like kinase 1 (Plk1), a member of the Polo-like kinase family, plays a critical role in regulating mitosis and cell cycle progression. Aberrant expression of Plk1 has been observed in a variety of human cancers, and it is known to be associated with tumorigenesis as well as poor prognosis in cancer patients. Unlike normal cells, some cancer cells are dependent on augmented Plk1 levels to remain viable and are killed when Plk1 function is attenuated.

One form of adoptive T cell therapy (ACT) consists of harvesting tumor infiltrating lymphocytes (TIL), screening and isolating TIL which display tumor antigen-specific T-cell receptors (TCR), expanding the isolated T cells in vitro, and reinfusing them into the patient for treatment. While highly active in the treatment of certain cancers (e.g., melanoma), current methods used to produce cancer-reactive T cells require significant time and may not adequately identify the desired TCRs which bind cancer targets.