Noriyuki Kasahara

389.3: Immortalized hypoimmune human mesenchymal stem cells for immunomodulation and wound healing.

Mária Barcová, Katrin Hacke, Akira Usui, Noriyuki Kasahara

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214.3: Gene editing with a novel binary retroviral vector system to reduce HLA class I allogenicity.

Sara Collins, Aneace Haddad, Trishna Patel, Katrin Hacke et autres

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Mesenchymal stem cell-mediated delivery boosts the efficacy of suicide gene therapy based on retroviral replicating vectors in peritoneally disseminated cancer

Shuji Kubo, Yuya Takeuchi, Emiko Sonoda, Nao Ogawa et autres

Retroviral replicating vectors (RRVs) hold promise for cancer gene therapy but face limitations due to their relatively low titers and susceptibility to inactivation by body fluids, limiting their application to intratumoral delivery. To overcome these challenges and target metastatic cancers, we investigated …

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Non-lytic viral immunotherapy induces long-term glioblastoma survival and tumor-specific immunity without eliciting an antiviral response

Alexander F. Haddad, Atul Saha, Sara Collins, Isabella Lovalvo et autres

Glioblastoma is a lethal brain tumor that is resistant to conventional therapies. Here we present a non-lytic replicating retrovirus (RRV) that delivers an IL-15-receptor-linked fusion protein (RLI) superagonist directly into glioblastoma cells, creating localized immunotherapy biofactories. In orthotopic mouse models, RRV-RLI dramatically …

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EXTH-77. An AI-engineered bioPROTAC reverses immortality of TERT promoter mutant tumors

Nicholas Stevers, Ellen Chen, Joshua H. Wu, Trishna S. Patel et autres

Abstract Telomerase Reverse Transcriptase promoter (TERTp) mutations enable tumor cell immortality in millions of cancer patients annually. TERTp mutations are the most common non-coding mutations across all cancers, including glioblastoma, oligodendroglioma, medulloblastoma, and high-grade meningioma. A multitude of TERTp mutations, including the …

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TIP-08. Trial in progress update: A phase 1/2 study of intracranial and intravenous multi-dosing of DB107-RRV (formerly Toca 511) and DB107-FC (5-fluorocytosine) in combination with radiation ± temozolomide (TMZ) in patients with newly diagnosed high-grade gliomas (HGGs)

M. Ashwin Reddy, Noriyuki Kasahara, Thomas C. Chen, David Piccioni et autres

Abstract BACKGROUND DB-107 RRV, a retroviral replicating vector, delivers a cytosine deaminase gene (yCD2) to tumor cells. This enzyme converts DB107-FC into chemotherapeutic agent 5-fluorouracil (5-FU), inducing tumor cell apoptosis. While prior studies targeted recurrent high-grade glioma (HGG) patients with DB107-RRV as …

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Data from Measles Oncolytic Virus as an Immunotherapy for Recurrent/Refractory Pediatric Medulloblastoma and Atypical Teratoid/Rhabdoid Tumor: Results from PNOC005

Bohyeon Yu, Cassie Kline, Owen Hoare, Jangham Jung et autres

AbstractPurpose: Pediatric recurrent medulloblastoma and atypical teratoid/rhabdoid tumor (ATRT) are largely incurable and warrant novel therapies. PNOC005 is a phase I clinical trial investigating the safety and tolerability of intratumoral or intrathecal administration of oncolytic measles virus (MV-NIS) in children and young …

Measles Oncolytic Virus as an Immunotherapy for Recurrent/Refractory Pediatric Medulloblastoma and Atypical Teratoid/Rhabdoid Tumor: Results from PNOC005

Bohyeon Yu, Cassie Kline, Owen Hoare, Jangham Jung et autres

PURPOSE: Pediatric recurrent medulloblastoma and atypical teratoid/rhabdoid tumor (ATRT) are largely incurable and warrant novel therapies. PNOC005 is a phase I clinical trial investigating the safety and tolerability of intratumoral or intrathecal administration of oncolytic measles virus (MV-NIS) in children and young …

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Abstract 474: IL-12 immunotherapy using a novel gene delivery platform for RNA payloads achieves effective antitumor responses without systemic toxicity in an aggressive CT26 murine cancer model

Laura Strauss, Akihito Inagaki, Stephanie Lees, Noriyuki Kasahara et autres

Background: IL-12 exhibits potent anti-tumor properties, which enhance cytolytic activity and tumor infiltration of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) and activates Th-1-type immune responses [1-2]. However, systemic administration of recombinant IL-12 protein is still a challenge due to …

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Non-lytic replicating viral delivery of an IL15 superagonist enhances antitumor immunity and extends survival in glioblastoma

Alexander F. Haddad, Atul Saha, Jordan Spatz, Sara Collins et autres

Abstract Glioblastoma (GBM) is the most lethal primary brain neoplasm due to its highly immunosuppressive microenvironment and resistance to conventional therapies. To overcome this challenge, we engineered a replicating retrovirus (RRV) to deliver a superagonist interleukin-15 receptor-linked fusion protein (RLI) directly to …

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P02.16.A IRF8-DRIVEN REPROGRAMMING OF THE IMMUNE MICROENVIRONMENT ENHANCES ANTI-TUMOR ADAPTIVE IMMUNITY AND REDUCES IMMUNOSUPPRESSION IN MURINE GLIOBLASTOMA

María Montoya, Stuart A. Collins, Pavlina Chuntova, Trishna S. Patel et autres

Abstract BACKGROUND Glioblastoma (GBM) has a highly immunosuppressive tumor immune microenvironment (TIME), largely mediated by myeloid-derived suppressor cells (MDSCs). Here, we utilized a retroviral replicating vector (RRV) to deliver Interferon Regulatory Factor 8 (IRF8), a master regulator of type 1 conventional dendritic …

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Interferon regulatory factor 8-driven reprogramming of the immune microenvironment enhances antitumor adaptive immunity and reduces immunosuppression in murine glioblastoma

Megan Montoya, Sara Collins, Pavlina Chuntova, Trishna S. Patel et autres

BACKGROUND: Glioblastoma (GBM) has a highly immunosuppressive tumor immune microenvironment (TIME), largely mediated by myeloid-derived suppressor cells (MDSCs). Here, we utilized a retroviral replicating vector (RRV) to deliver Interferon Regulatory Factor 8 (IRF8), a master regulator of type 1 conventional dendritic cell …

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