Development of chimeric antigen receptor (CAR)-T cells targeting A56 viral protein implanted by oncolytic virus.

To address the challenge of solid tumor targeting in CAR-T therapy, we utilized the A56 antigen, which is uniquely expressed on a diverse range of cancer cells following the systemic administration of an oncolytic vaccinia virus (OVV). Immunohistochemical assays precisely confirmed exclusive localization of A56 to tumor tissues. In vitro studies demonstrated a distinct superiority of A56-dependent CAR-T cytotoxicity across multiple cancer cell lines. Building on these in vitro observations, we strategically administered A56 CAR-T cells, OVV, and hydroxyurea (HU) combination in HCT-116 tumor-bearing non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, leading to a significant reduction in tumor size and an extended time to progression. Consequently, A56-targeting combinatorial immunotherapy provides the benefit of reducing inadvertent CAR-T effects on normal cells while preserving its effectiveness against cancer cells. Furthermore, our approach of implanting A56 via OVV on tumors facilitates a wide therapeutic application of CAR-T cells across various solid tumors.

Anatomical insights of the mylohyoid for clinical procedures in dentistry.

INTRODUCTION: The purpose of this study is to provide useful data by conducting a comprehensive study of the mylohyoid muscle and its related structures. MATERIALS AND METHODS: Fifty-eight mandibles and 30 mylohyoid muscles from Korean adult cadavers were used. The shape and location of the mylohyoid line were analyzed by using digital calipers. The mylohyoid muscle and its herniation were observed using ultrasonography. After dissection, morphometric measurements of the muscle and herniation were conducted. The distribution pattern of the nerve to mylohyoid muscle was confirmed. RESULTS: The proportion of the distance between the cementoenamel junction and the mylohyoid line decreased from the mesiolingual cusp of the mandibular first molar (1:0.57) to the distolingual cusp of the mandibular second molar (1:0.41). The mylohyoid muscle was large, thick, and deep in men. Herniation was observed in 16 (53.3%) cases, and it was concentrated in the anterior one-third (52.2%) of the muscle. The richest arborization of the nerve to mylohyoid muscle was in the middle one-third (52.9%) of the muscle. CONCLUSIONS: The results of the mylohyoid line can be applied in the reconstruction of the occlusal plane in edentulous patients. Differences between the sexes should be considered in the morphological characteristics of the mylohyoid muscle. Differential diagnosis of herniation is particularly important in the anterior one-third of the muscle. In the case of treatment with botulinum toxin in the mylohyoid muscle, it is recommended to inject into the middle one-third area considering the depth and thickness of the muscle in that area.

Relationships among Perceptions of Dying Well, Attitudes toward Advance Directives, and Preferences for Advance Directives among Elderly Living Alone.

Purpose: This study investigated awareness of dying well, as well as attitudes and preferences toward advance directives (ADs), among elderly individuals who lived alone. Methods: The participants were 173 elderly people living alone. Data were collected from July 2019 to September 2019 using questionnaires on perceptions of dying well, awareness of advance directives, and general characteristics. Results: The majority of participants (68.2%) stated that they had never heard of advance directives. The information they requested to include in their advance directives mostly involved decisions on pain treatment, such as the use of analgesic drugs in the final stages of a terminal disease. Perceptions of dying well were statistically significantly different according to age and education. Conclusion: This study discussed the attitudes and preferences of elderly living alone regarding advance directives to provide basic resources for the systematic and active use of advance directives.

Preclinical safety evaluation of hepatic arterial infusion of oncolytic poxvirus.

PURPOSE: Oncolytic poxvirus has shown promise in treating various solid tumors, such as liver cancer, and administration of oncolytic poxvirus via the hepatic artery may provide more survival benefits than other routes of administration. However, there is a lack of safety information to guide the application of hepatic arterial infusion (HAI) of oncolytic poxvirus in human studies. To investigate the acute and chronic toxicity of HAI administration of oncolytic poxvirus in animals and provide safety information for future human studies. METHODS: VVtk-, a vaccinia poxvirus with inactivated thymidine kinase gene, was administered via HAI to rabbits with normal liver function under angiography (1×108 or 1×109 pfu), and rats with N-nitrosomorpholine-induced precancerous liver cirrhosis under open surgery (1×108 pfu). Body weights and survival were monitored and blood samples were collected for hematological and biochemical tests. Distribution of A56 (a specific marker for poxvirus infection) in rabbit organs was evaluated using immunofluorescence assays. RESULTS: HAI of high doses of VVtk- did not cause any acute or chronic changes in body weight, survival or in biochemical, hematological tests in the 2 animal models, and none of the changes showed dose dependency (in rabbit study), or were influenced by liver cirrhosis (in rat study). A56 was not detected in any of the major rabbit organs. CONCLUSION: HAI may provide a safe alternative route of oncolytic poxvirus administration for human studies.