Answer the question..I'm not making it up..For some more information check in with research gate.net as I did last year. Dr Anthony K Park of the City Of Hope has 33 publication pertaining to everything from CF33, Oncarlytics and associated topics. Then come back to me with a considered opinion, not another down ramping stunt..
While chimeric antigen receptor (CAR) T cells have received FDA approvals in treating hematological malignancies, clinical responses of CAR T cells for solid tumors have been underwhelming. Intense investigation is underway to improve CAR T cells trafficking, persistence and efficacy. Interleukin-12 (IL-12) is a potent inflammatory cytokine that re...
Background: Gastric cancer (GC) that metastasizes to the peritoneum is fatal. CF33 and its genetically modified derivatives show cancer selectivity and oncolytic potency against various solid tumors. CF33-hNIS and CF33-hNIS-antiPDL1 have entered phase I trials for intratumoral and intravenous treatments of unresectable solid tumors (NCT05346484) a...
430 Background: No effective therapy exists for peritoneal metastases (PM) from gastric cancer (GC), which remain fatal within months of diagnosis. We investigated a novel chimeric oncolytic virus platform, CF33-OV, for its anti-cancer potential against peritoneal cancer cells from GC patients. Methods: We prospectively collected fresh ascites or p...
428 Background: Peritoneal carcinomatosis (PC) is a deadly end-stage manifestation of gastric cancer (GC). CF33, a chimeric oncolytic virus, and its genetically modified derivatives have shown exclusive cancer selectivity and oncolytic potency against various solid tumors. Intravenous and intratumoral CF33-hNIS and CF33-hNIS-antiPDL1 have entered p...
Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited T cell trafficking, persistence, and durable anti-tumor activity in solid tumor microenvironments. However, these challenges can be largely overcome by relatively unconstrained synthetic engineering strategies, which are being harnessed to improve solid tumor CAR T...
Immunotherapeutic strategies that combine oncolytic virus (OV) and immune checkpoint inhibitors have the potential to overcome treatment resistance in pancreatic ductal adenocarcinoma (PDAC), one of the least immunogenic solid tumors. Oncolytic viral chimera, CF33-hNIS-antiPDL1 genetically modified to express anti-human PD-L1 antibody and CF33-hNIS...
Pancreatic cancer resistance to immunotherapies is partly due to deficits in tumor-infiltrating immune cells and stromal density. Combination therapies that modify stroma and recruit immune cells are needed. Vitamin D analogues like calcipotriol (Cal) decrease fibrosis in pancreas stroma, thus allowing increased chemotherapy delivery. OVs infect, r...
Peritoneal carcinomatosis of gastrointestinal malignancies remains fatal. CF33-hNIS-antiPDL1, a chimeric orthopoxvirus expressing the human sodium iodide symporter (hNIS) and anti-human programmed death-ligand 1 antibody, has demonstrated robust preclinical activity against pancreatic adenocarcinoma (PDAC). We investigated the ability of CF33-hNIS-...
Chimeric antigen receptor (CAR) T cell therapy has led to impressive clinical responses in patients with hematological malignancies; however, its utility in patients with solid tumors has been limited. While CAR T cells for the treatment of advanced prostate cancer are being clinically evaluated and are anticipated to show bioactivity, their safety...
Introduction: We investigated a novel oncolytic virus, CF33-hNIS-antiPDL1, which has shown robust preclinical activity against numerous solid tumors, for its ability to track and kill distant peritoneal metastases after local virus administration in vivo. Methods: In this study, we used CF33-hNIS-antiPDL1, a replication competent orthopoxviral chim...
Oncolytic viruses infect, replicate in, and kill cancer cells, leaving normal cells unharmed; they also recruit and activate immune cells against tumor cells. While clinical indications for viroimmunotherapy are growing, barriers to widespread treatment remain. Ensuring real-time tracking of viral replication and resulting anti-tumor immune respons...
Chimeric antigen receptor (CAR) T cell therapy has led to impressive clinical responses in patients with hematological malignancies; however, its effectiveness in patients with solid tumors has been limited. While CAR T cells for the treatment of advanced prostate and pancreas cancer, including those targeting prostate stem cell antigen (PSCA), are...
Although it is known that oncolytic viruses can inflame and recruit immune cells to otherwise immunosuppressed tumor microenvironments, the influence of the antiviral immune response on antitumor immunity is less clear across viral platforms and tumor types. CF33 is a recombinant orthopoxvirus backbone effective against colon cancer. We tested deri...
Chimeric antigen receptor (CAR) T cell therapy has led to impressive clinical responses in patients with hematological malignancies; however, its utility in patients with solid tumors has been limited. While CAR T cells for the treatment of advanced prostate cancer are being clinically evaluated and are anticipated to show bioactivity, their safety...
Oncolytic viroimmunotherapy is an exciting modality that can offer lasting anti-tumor immunity for aggressive malignancies like colon cancer. The impact of oncolytic viruses may be extended by combining them with agents to prime a tumor for viral susceptibility. This study investigates vitamin D analogue as an adjunct to oncolytic viral therapy for...
Chimeric antigen receptor (CAR)-engineered T cell therapy for solid tumors is limited by the lack of both tumor-restricted and homogeneously expressed tumor antigens. Therefore, we engineered an oncolytic virus to express a nonsignaling, truncated CD19 (CD19t) protein for tumor-selective delivery, enabling targeting by CD19-CAR T cells. Infecting t...
Triple-negative breast cancer is the most aggressive subtype of breast cancer and is difficult to treat. Breast cancer is considered to be poorly immunogenic and hence is less responsive to immunotherapies. We tested whether the oncolytic poxvirus CF33-hNIS-ΔF14.5 could modulate tumor immune microenvironment and make the tumors responsive to the im...
Background: Peritoneal carcinomatosis (PC) from pancreatic ductal adenocarcinoma (PDAC) is fatal. Our preclinical study presents an effective treatment against PDAC PC employing a novel oncolytic viral agent, CF33-hNIS-antiPDL1. Study design: CF33-hNIS-antiPDL1 is a genetically engineered chimeric orthopoxvirus, CF33, armed with the human Sodium...
Chimeric antigen receptor (CAR)-engineered T cell therapy for solid tumors is limited by the lack of tumor-restricted and homogeneous expression of tumor antigens 1,2 . Therefore, we engineered an oncolytic virus to express a non-signaling, truncated CD19 (CD19t) protein for tumor-selective delivery, enabling targeting by CD19-specific CAR T cells....
Background: Pancreatic ductal adenocarcinoma (PDAC) has been increasing by 0.5% per year in the United States. PDAC portends a dismal prognosis and novel therapies are needed. This study describes the generation and characterization of a novel oncolytic chimeric orthopoxvirus for the treatment of pancreatic cancer. Methods: After chimerization a...
Introduction This study hypothesizes that a novel oncolytic chimeric orthopoxvirus CF33-Fluc is imageable and targets colorectal cancer cells (CRC). Methods A novel chimeric orthopoxvirus (CF33) was constructed. The thymidine kinase locus was replaced with firefly luciferase (Fluc) to yield a recombinant virus – CF33-Fluc. In vitro cytotoxicity an...
Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we have optimized HER2...
Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell an...
Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer should be amenable to CAR-based immunotherapy given that several tumor antigens, including prostate stem-ce...
Adoptive transfer of chimeric antigen receptor (CAR)-engineered T cells has demonstrated robust and durable clinical efficacy in patients with CD19+ B-cell malignancies. Broader application of this approach to brain and other advanced solid tumors is an immediate goal for the field and is presently under intense investigation. In 2014, 40,000 indiv...
Prostate Cancer (PCa) is the third most common cancer type in the United States, with over 200,000 new cases projected to be diagnosed this year. In approximately 80% of PCa patients, tumor phenotype includes overexpression of prostate stem cell antigen, or PSCA. Furthermore, PSCA is expressed on nearly 100% of bone metastatic prostate cancers, mak...
Adoptive transfer of chimeric antigen receptor (CAR)-engineered T cells has demonstrated robust and durable clinical efficacy in patients with CD19+ B cell malignancies. Broader application of this approach to brain and other advanced solid tumors is an immediate goal for the field and is presently under intense investigation. In 2014, 40,000 indiv...
Glioblastoma multiforme (GBM) is the most common brain tumor, with a poor prognosis of less than 14 months after initial diagnosis. Gene amplification and mutation of epidermal growth factor receptor (EGFR) are frequently observed in primary GBM. The most common variant of EGFR, known as EGFRvIII, is expressed in approximately 30% of GBM patients,...
Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ9-THC treatment on mouse resistance to systemic Candida albicans (C. al...
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