Daejin Lim, Kwangsoo Kim, Taner Duysak, EunA. So, Jae-Ho Jeong, Hyon E. Choy
{"title":"Bacterial cancer therapy using the attenuated fowl-adapted Salmonella enterica serovar Gallinarum","authors":"Daejin Lim, Kwangsoo Kim, Taner Duysak, EunA. So, Jae-Ho Jeong, Hyon E. Choy","doi":"10.1016/j.omto.2023.100745","DOIUrl":"https://doi.org/10.1016/j.omto.2023.100745","url":null,"abstract":"","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"158 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135326269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francisca Cristi, Maiah Walters, Nashae Narayan, Kate Agopsowicz, Mary M. Hitt, Maya Shmulevitz
{"title":"Improved oncolytic activity of a reovirus mutant that displays enhanced virus spread due to reduced cell attachment","authors":"Francisca Cristi, Maiah Walters, Nashae Narayan, Kate Agopsowicz, Mary M. Hitt, Maya Shmulevitz","doi":"10.1016/j.omto.2023.100743","DOIUrl":"https://doi.org/10.1016/j.omto.2023.100743","url":null,"abstract":"","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"160 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135326263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yun Yang, He Wu, Yan Yang, Yan Kang, Runjia He, Bei Zhou, Huaizu Guo, Jing Zhang, Jianqin Li, Chunpo Ge, Tianyun Wang
{"title":"Dual blockade of CD47 and CD24 signaling using a novel bispecific antibody fusion protein enhances macrophage immunotherapy","authors":"Yun Yang, He Wu, Yan Yang, Yan Kang, Runjia He, Bei Zhou, Huaizu Guo, Jing Zhang, Jianqin Li, Chunpo Ge, Tianyun Wang","doi":"10.1016/j.omto.2023.100747","DOIUrl":"https://doi.org/10.1016/j.omto.2023.100747","url":null,"abstract":"","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"9 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135412582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annie Yang, Zhifang Zhang, Shyambabu Chaurasiya, Anthony K Park, Jianming Lu, Sang-In Kim, Hannah Valencia, Yuman Fong, Yanghee Woo
{"title":"Peritoneal-directed chimeric oncolytic virus CF17 prevents malignant ascites and improves survival in gastric cancer peritoneal metastases.","authors":"Annie Yang, Zhifang Zhang, Shyambabu Chaurasiya, Anthony K Park, Jianming Lu, Sang-In Kim, Hannah Valencia, Yuman Fong, Yanghee Woo","doi":"10.1016/j.omto.2023.100734","DOIUrl":"10.1016/j.omto.2023.100734","url":null,"abstract":"<p><p>Gastric cancer (GC) peritoneal metastasis (PM) is fatal without effective therapy. We investigated CF17, a new replication-competent chimeric poxvirus, against GC cell lines <i>in vitro</i> and PM in an aggressive GCPM mouse model. We performed viral proliferation and cytotoxicity assays on intestinal-type and diffuse-type human GC cell lines following CF17 treatment. At lower MOIs of 0.01, 0.1, there was >80% killing in most cell lines, while in the more aggressive cell lines, killing was seen at higher MOIs of 1.0 and 10.0. We observed reduced peritoneal tumor burden and prolonged survival with intraperitoneal (i.p.) CF17 treatment in nude mice implanted with the resistant GC cell line. At day 91 after treatment, seven of eight mice were alive in the CF17-treated group vs. one of eight mice in the control group. CF17 treatment inhibited ascites formation (0% vs. 62.5% with PBS). Thus, CF17 efficiently infected, replicated in, and killed GC cells in a dose- and time-dependent manner <i>in vitro</i>. <i>In vivo</i>, i.p. CF17 treatment exhibited robust antitumor activity against an aggressive GCPM model to decrease tumor burden, improve survival, and prevent ascites formation. These preclinical results inform the design of future clinical trials of CF17 for peritoneal-directed therapy in GCPM patients.</p>","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"31 ","pages":"100734"},"PeriodicalIF":5.7,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kelly M Makielski, Aaron L Sarver, Michael S Henson, Kathleen M Stuebner, Antonella Borgatti, Lukkana Suksanpaisan, Caitlin Preusser, Alexandru-Flaviu Tabaran, Ingrid Cornax, M Gerard O'Sullivan, Andrea Chehadeh, Donna Groschen, Kelly Bergsrud, Sara Pracht, Amber Winter, Lauren J Mills, Marc D Schwabenlander, Melissa Wolfe, Michael A Farrar, Gary R Cutter, Joseph S Koopmeiners, Stephen J Russell, Jaime F Modiano, Shruthi Naik
{"title":"Neoadjuvant systemic oncolytic vesicular stomatitis virus is safe and may enhance long-term survivorship in dogs with naturally occurring osteosarcoma.","authors":"Kelly M Makielski, Aaron L Sarver, Michael S Henson, Kathleen M Stuebner, Antonella Borgatti, Lukkana Suksanpaisan, Caitlin Preusser, Alexandru-Flaviu Tabaran, Ingrid Cornax, M Gerard O'Sullivan, Andrea Chehadeh, Donna Groschen, Kelly Bergsrud, Sara Pracht, Amber Winter, Lauren J Mills, Marc D Schwabenlander, Melissa Wolfe, Michael A Farrar, Gary R Cutter, Joseph S Koopmeiners, Stephen J Russell, Jaime F Modiano, Shruthi Naik","doi":"10.1016/j.omto.2023.100736","DOIUrl":"10.1016/j.omto.2023.100736","url":null,"abstract":"<p><p>Osteosarcoma is a devastating bone cancer that disproportionally afflicts children, adolescents, and young adults. Standard therapy includes surgical tumor resection combined with multiagent chemotherapy, but many patients still suffer from metastatic disease progression. Neoadjuvant systemic oncolytic virus (OV) therapy has the potential to improve clinical outcomes by targeting primary and metastatic tumor sites and inducing durable antitumor immune responses. Here we describe the first evaluation of neoadjuvant systemic therapy with a clinical-stage recombinant oncolytic vesicular stomatitis virus (VSV), VSV-IFNβ-NIS, in naturally occurring cancer, specifically appendicular osteosarcoma in companion dogs. Canine osteosarcoma has a similar natural disease history as its human counterpart. VSV-IFNβ-NIS was administered prior to standard of care surgical resection, permitting microscopic and genomic analysis of tumors. Treatment was well-tolerated and a \"tail\" of long-term survivors (∼35%) was apparent in the VSV-treated group, a greater proportion than observed in two contemporary control cohorts. An increase in tumor inflammation was observed in VSV-treated tumors and RNA-seq analysis showed that all the long-term responders had increased expression of a T cell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNβ-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity.</p>","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"31 ","pages":"100736"},"PeriodicalIF":5.7,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107591785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models.","authors":"Kosuke Inoue, Hirotaka Ito, Miwako Iwai, Minoru Tanaka, Yoshiyuki Mori, Tomoki Todo","doi":"10.1016/j.omto.2023.07.002","DOIUrl":"https://doi.org/10.1016/j.omto.2023.07.002","url":null,"abstract":"<p><p>A complete resection of tongue cancer is often difficult. We investigate the usefulness of administering G47Δ (teserpaturev), a triple-mutated oncolytic herpes simplex virus type 1, prior to resection. G47Δ exhibits good cytopathic effects and replication capabilities in all head and neck cancer cell lines tested. In an orthotopic SCCVII tongue cancer model of C3H/He mice, an intratumoral inoculation with G47Δ significantly prolongs the survival. Further, mice with orthotopic tongue cancer received neoadjuvant G47Δ (or mock) therapy with or without \"hemilateral\" resection, the maximum extent avoiding surgical deaths. Neoadjuvant G47Δ and resection led to 10/10 survival (120 days), whereas the survivals for G47Δ alone and resection alone were 6/10 and 5/10, respectively: all control animals died by day 11. Furthermore, 100% survival was achieved with neoadjuvant G47Δ therapy even when the resection area was narrowed to \"partial,\" providing insufficient resection margins, whereas hemilateral resection alone caused death by local recurrence in half of the animals. G47Δ therapy caused increased number of tumor-infiltrating CD8<sup>+</sup> and CD4<sup>+</sup> cells, increased F4/80<sup>+</sup> cells within the residual tongues, and increased expression of immune-related genes in and around the tumor. These results imply that neoadjuvant use of G47Δ is useful for preventing local recurrence after tongue cancer surgery.</p>","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"30 ","pages":"72-85"},"PeriodicalIF":5.7,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b9/e3/main.PMC10423690.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10366442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pierre V M Trehin, Geisler Muñoz-Guamuro, Wilfried Weber
{"title":"Dynamic fine-tuning of CAR-T cell therapy.","authors":"Pierre V M Trehin, Geisler Muñoz-Guamuro, Wilfried Weber","doi":"10.1016/j.omto.2023.06.001","DOIUrl":"https://doi.org/10.1016/j.omto.2023.06.001","url":null,"abstract":"","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"30 ","pages":"14-15"},"PeriodicalIF":5.7,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9879916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Norris Lam, Richard Finney, Shicheng Yang, Stephanie Choi, Xiaolin Wu, Lauren Cutmore, Jorge Andrade, Lei Huang, Christina Amatya, Margaret Cam, James N Kochenderfer
{"title":"Development of a bicistronic anti-CD19/CD20 CAR construct including abrogation of unexpected nucleic acid sequence deletions.","authors":"Norris Lam, Richard Finney, Shicheng Yang, Stephanie Choi, Xiaolin Wu, Lauren Cutmore, Jorge Andrade, Lei Huang, Christina Amatya, Margaret Cam, James N Kochenderfer","doi":"10.1016/j.omto.2023.07.001","DOIUrl":"https://doi.org/10.1016/j.omto.2023.07.001","url":null,"abstract":"<p><p>To address CD19 loss from lymphoma after anti-CD19 chimeric antigen receptor (CAR) T cell therapy, we designed a bicistronic construct encoding an anti-CD19 CAR and an anti-CD20 CAR. We detected deletions from the expected bicistronic construct sequence in a minority of transcripts by mRNA sequencing. Loss of bicistronic construct transgene DNA was also detected. Deletions of sequence were present at much higher frequencies in transduced T cell mRNA versus gamma-retroviral vector RNA. We concluded that these deletions were caused by intramolecular template switching of the reverse transcriptase enzyme during reverse transcription of gamma-retroviral vector RNA into transgene DNA of transduced T cells. Intramolecular template switching was driven by repeated regions of highly similar nucleic acid sequence within CAR sequences. We optimized the sequence of the bicistronic CAR construct to reduce repeated regions of highly similar sequences. This optimization nearly eliminated sequence deletions. This work shows that repeated regions of highly similar nucleic acid sequence must be avoided in complex CAR constructs. We further optimized the bicistronic construct by lengthening the linker of the anti-CD20 single-chain variable fragment. This modification increased CD20-specific interleukin-2 release and reduced CD20-specific activation-induced cell death. We selected an optimized anti-CD19/CD20 bicistronic construct for clinical development.</p>","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"30 ","pages":"132-149"},"PeriodicalIF":5.7,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/9a/main.PMC10465854.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10153670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}