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T cell immunotherapy is used in the treatment of various pathologies – including cancers and infections. Current therapies employ chimeric antigen receptors (CARs) consisting of the intracellular fragment of CD3-zeta as the signaling domain with varied combinations of co-stimulatory, transmembrane, spacer/hinge, and extracellular targeting domains. While effective in treating hematological malignancies, CAR T cells need to be activated through T cell receptor (TCR) activation.

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. 

The treatment of cancer using immunotherapies has garnered substantial attention and excitement considering the clinical benefits observed in patient populations previously refractory to treatment. Tumor infiltrating T cells can significantly impact cancer progression and immunotherapy response; however, immunosuppressive tumor microenvironments can impede antitumor T cell induction, trafficking, and local activity. Thus, personalized immunotherapy approaches have shown limited efficacy against most solid tumors.

The chemokine receptor, CCR4 is a seven transmembrane G protein-coupled cell surface receptor molecule with selective expression on cells of the hematopoietic system. In adult T cell leukemia (ATL), the cell-surface expression of CCR4 on leukemic cells has been found to be nearly universal. Therefore, a CCR4-directed chimeric antigen receptor (CAR) -cell may provide an effective therapeutic against ATL.

Mesothelioma is an aggressive cancer covering anatomic surfaces (e.g. lining of the lungs, heart, abdomen, etc.) that resists multi-modality therapies. Regional recurrence of mesothelioma from residual tumor cells prevents long-term benefits after surgical resection. Furthermore, there is no clinical consensus on intracavitary adjuvants that are effective in extending the tumor reduction effect of surgery.

RNA interference (RNAi) is a biological response to double-stranded RNA that regulates expression of protein-coding genes and is a natural mechanism for gene silencing. Delivery of short, interfering RNA (siRNA) leads to RNAi of the targeted genes. 

In medical diagnostic procedures for examining the cervix and the tissues of the vagina and vulva, long working-distance (-30 cm) lighted binocular microscopes (colposcope) that provide up to 25x optical magnification are used to create an illuminated magnified view. Speculum dilations can give rise to specular reflections from the tissue surface, causing physicians to overlook possible abnormalities – thus decreasing the quality of a colposcopy. 

Adoptive cell therapy (ACT) using tumor-specific T cells can produce positive clinical responses in some cancer patients. Nevertheless, several obstacles to the successful use of ACT for the treatment of cancer and other conditions remain. For example, one or more of the in vivo persistence, survival, and antitumor activity of tumor-specific T cells can, in some cases, decrease following adoptive transfer. Accordingly, there is a need for methods of obtaining a robust population of tumor-specific T cells for ACT.

Cancer is the second leading cause of death worldwide. The primary cause of mortality from cancer is metastasis. While the underlying mechanisms of cancer metastasis are still being unraveled, the gp78 protein involved in ER-associated degradation (ERAD) appears to play a role in metastasis in sarcoma. Targeting gp78 may be a therapeutic option in cancer treatment.

Primary liver tumors and secondary hepatic malignancies are among the leading causes of cancer-related deaths. Liver metastases account for 95% of all hepatic cancers, and the liver is the most common site for organ metastasis in the body. The gut microbiome serves an important role in antitumor immunity regulating the efficacy of chemo- and immunotherapies. The liver is exposed to gut bacteria through blood from the intestine, with 70% of the whole liver’s blood supply coming from intestinal blood. Changes in the commensal microbiome may affect immune cell function in the liver.