POSTER PRESENTATIONS – STUDENTS
EFFECT OF DUAL CAR-NK CELL (ANTI-MCAM + ANTI-ROR1) IMMUNOTHERAPY AGAINST OSTEOSARCOMA Diane Hurwitz, Alexandra Sobocinski, Thomas Hefele, Shiori Eguchi, Hai Hoang, Hongwen Zhu, Wen Luo, Mitchell S. Cairo, Helen E. Pope; Tulane University School of Medicine, New Orleans, LA.
Introduction: Both melanoma cell adhesion molecule (MCAM/CD146) and receptor tyrosine kinase-like orphan receptor 1 (ROR1) are potential targets for osteosarcoma therapy because high expression of both can be associated with poor patient outcomes. Natural killer (NK) cells recognize and eliminate cancer cells in a process that is markedly enhanced through chimeric antigen receptor (CAR) expression, providing a potential for CAR-NK cell therapeutics with defined specificity. Thus, our objective is to investigate how anti- MCAM combined with anti-ROR1 CAR-NK cell (dual CAR-NK) enhances the inherent NK-osteosarcoma cytotoxicity. In doing so, we hope to create a more efficacious treatment for osteosarcoma in cell lines that are sensitive to MCAM and ROR1. Methods/Results: Peripheral blood mononuclear cells (PBMCs) were expanded into NK cells ex vivo. Anti-MCAM, anti-ROR1, and dual CAR-NK cells with both anti-MCAM and anti-ROR1 were generated by non-viral electroporation of anti-MCAM and anti- ROR1 CAR mRNA into expanded NK cells. CAR-NK cytotoxicity was evaluated in vitro by luciferase-
based cytotoxicity assay. MCAM and ROR1 expression in osteosarcoma cell lines and the electroporated CAR-NK cells were validated by flow cytometry. mRNA electroporation successfully generated ROR1 CAR and MCAM CAR individually as well as dual CAR with both MCAM and ROR1 CAR on ex vivo expanded NK cells. The dual CAR has higher in vitro cytotoxic activity than MCAM CAR or ROR1 CAR alone at an E:T ratio of 0.1:1, while the MCAM CAR and the ROR1 CAR both still have an increased cytotoxicity compared to the mock. At the E:T ratios of 0.2:1 and 0.5:1, both the dual CAR and the MCAM CAR had an increased cytotoxicity compared to the mock and the ROR1 CAR. The MCAM CAR, ROR1 CAR, and dual CAR expressing NK cells all have increased granzyme B secretions compared to the mock, with the MCAM CAR and the dual CAR having significantly higher increases than the ROR1 CAR and the dual CAR having an even higher increase than the MCAM CAR. Discussion: Preliminary data shows that both the MCAM CAR alone and the dual CAR are more likely to have a cytotoxic effect against osteosarcoma than the ROR1 CAR alone.
UNRAVELING THE COMPLEXITY OF FIBROLAMELLAR CARCINOMA: AN UNFORTUNATE CASE OF RARE LIVER CANCER Donnell White, Christopher Chedid, Sudhir K. Aggarwal; Louisiana State University School of Medicine, New Orleans, LA.
Introduction: Fibrolamellar carcinoma (FLC) is a rare variant of hepatocellular carcinoma (HCC) that primarily affects young individuals without underlying liver disease such as cirrhosis or hepatitis. While FLC shares some morphological features with conventional HCC, it is distinguished by its unique clinical presentation, histological appearance, and molecular profile, particularly the DNAJB1-PRKACA fusion gene. This case highlights the complexities of diagnosing and treating FLC and the challenges posed by treatment-related complications.
Case: A 23-year-old female patient with no significant past medical history presented with nausea and intermittent vomiting. An MRI of the abdomen revealed a 16 cm right hepatic mass with a worrisome right lower lobe pulmonary nodule measuring 1 cm. The patient underwent liver biopsy, confirming malignancy with tumor cells positive for arginase and keratin 7, focally weakly positive for CD68, and a 3-5% Ki-67 labeling index. The DNAJB1-PRKACA gene rearrangement was confirmed via FISH study, supporting the diagnosis of fibrolamellar carcinoma. 67
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