Biology subjects

Cannon, M. J.

Publications and source records attributed to Cannon, M. J..

4 recordsLinked to original sources

bioRxiv2026

dgiLIT: A Method for Prioritization and AI Curation of Drug-Gene Interactions

IMPORTANCEThe Drug-Gene Interaction Database (DGIdb) has a long history of driving hypothesis generation for biomedical research through the careful curation of drug-gene interaction data from primary and secondary sources with supporting literature. Recent advances in large-language model (LLM) and artificial intelligence (AI) technologies have enabled new paradigms for knowledge extraction and biocuration. The accelerating growth of biomedical literature presents a significant challenge for maintaining up-to-date interaction data. With more than 38 million citations indexed in PubMed alone, new strategies must evolve to identify and incorporate new interaction data into DGIdb. OBJECTIVEIdentify new cost-effective AI curation strategies for incorporating new drug-gene interactions into DGIdb. METHODSWe present a methodology that leverages deterministic natural language processing techniques, existing harmonization frameworks, and AI-assisted curation to systematically narrow the literature space and identify new drug-gene interactions from published studies for inclusion in DGIdb. RESULTSWe demonstrate the use of lemmatization to prioritize a set of 100 abstracts containing high amounts of interaction words for downstream AI curation. From our set of abstracts, we were then able to identify 137 drug-gene interactions via an AI curation task, with 121 (88.3%) of these interactions being completely novel to DGIdb. A human expert evaluator reviewed this interaction set and was able to validate 134 of 137 (97.8%) interactions as being valid based on the text provided. CONCLUSIONTaken together, our results highlight a promising, cost-effective method of ingesting new interactions into DGIdb.

bioinformatics↗

bioRxiv2025

Pancreatic tumor microenvironment reprogramming via alloantigen-expressing virotherapy elicits tumor rejection and improves immunotherapy response

Pancreatic ductal adenocarcinoma (PDAC), the most common malignant type of pancreatic cancer, is characterized by a dense desmoplastic stroma, low neoantigen burden, and a highly immunosuppressive tumor microenvironment (TME), which severely limit cytotoxic T-cell infiltration and the efficacy of immune therapies. Here, we present a novel strategy harnessing acute transplant rejection mechanisms by employing a recombinant oncolytic rVMG vector engineered to express the murine H-2Kk MHC class I alloantigen (rVMG-H-2Kk), thereby inducing tumor-specific antigenic mismatch responses. In vitro, rVMG-H-2Kk exhibited strong replication and cytolytic activity while inducing cell surface expression of both H-2Kk and endogenous H-2Kb, in addition to upregulation of antigen presentation genes ({beta}2-microglobulin, Tap1, and Tapbp). In two independent immunocompetent PDAC models, intratumoral and systemic delivery of rVMG-H-2Kk delayed tumor progression and prolonged survival. Multiplex immunohistochemistry and immunophenotyping revealed substantial TME remodeling, marked by increased effector T-cell infiltration, regulatory T-cell depletion, and reduced fibrosis. Spatial transcriptomics further showed compartment-specific immune activation and epithelial metabolic reprogramming, corroborating with enhanced tumor immunogenicity. Despite these effects, rVMG-H-2Kk also induced compensatory immunosuppressive pathways, including upregulation of antiviral response genes and immune checkpoint receptors such as PDL-2. Importantly, combination therapy with rVMG-H-2Kk and murine checkpoint blockade (anti-PD-1 and anti-CTLA-4) drastically improved survival than checkpoint blockade alone. Strikingly, surviving mice resisted tumor rechallenge, indicating the establishment of durable antitumor memory. Collectively, these findings establish rVMG-H-2Kk as a novel immunotherapeutic platform capable of converting immune-cold tumors into immune-hot, sensitizing tumors to immune checkpoint inhibitors, and establishing durable antitumor immunity in PDAC. One Sentence SummaryOncolytic virus-based delivery of an alloantigen improves antitumor immunity and synergizes with immune checkpoint inhibitors in pancreatic cancer. Significance statementDelivery of murine alloantigens via an engineered oncolytic vesiculovirus, combined with immune checkpoint blockade, overcomes immunosuppressive barriers and establishes durable antitumor immunity in PDAC.

cancer biology↗

bioRxiv2022

In vivo Safety and Immunoactivity of Oncolytic Jurona Virus in Hepatocellular Carcinoma: A Comprehensive Proteogenomic Analysis

Oncolytic viruses can effectively unwrap a multimodal anti-tumor activity, encompassing a selective tumor cell killing and promoting a systemic anti-tumor immunity, making them a formidable foe against cancer. Among these, several members of the Rhabdoviridae family are particularly attractive as oncolytic agents due to their natural tumor selectivity and non-pathogenicity in humans. In this study, we demonstrated that intratumorally (IT) administration of Jurona virus (JURV), a novel oncolytic Rhabdovirus, induces dynamic tumor regression in human HCC xenograft and syngeneic models. Our data shows that IT injections of JURV trigger the recruitment and activation of cytotoxic T (CTLs) and decrease the tumor-associated macrophages (TAM) infiltration leading to tumor growth delay in both local and distant murine HCC tumors in a syngeneic model. Moreover, when administered concomitantly, JURV and anti-PD-1 therapy profoundly modulate the tumor microenvironment (TME) via enhanced infiltration of CTLs, suggesting that immune checkpoint blockade therapy could potentiate the immunomodulatory effect of JURV and potentially provide durable anti-tumor immunity. Our analysis of the molecular and cellular mechanism of JURV-medicated anti-cancer activity unveiled that JURV and anti-PD-1 antibodies activate different effectors of the immune system but have complementary anti-tumor activities. Furthermore, our results indicate that the abscopal effect induced by JURV is likely mediated by the mechanism regulating the T helper cell responses. Our work supports the further development of JURV as a novel immunovirotherapy platform for hepatocellular carcinoma.

immunology↗

bioRxiv2022

Repurposing Live Attenuated Trivalent MMR Vaccine as Cost-effective Cancer Immunotherapy

Despite its rising promise, cancer immunotherapy remains out of reach for many patients because of the extensive cost of manufacturing immunotherapy products. In this study, we show that intratumoral injections of the trivalent measles, mumps, and rubella (MMR) live attenuated viral vaccine (LAVs) modulates a potent cytotoxic T-cell antitumor immune response, resulting in tumor growth inhibition and improved survival in syngeneic mouse models of hepatocellular carcinoma and colorectal cancer. Using an integrated transcriptomic and proteomic approach, we demonstrated that mechanistically, MMR exerts its antitumor activity by priming innate and adaptive antitumor immune responses, leading to immunologically coordinated cancer cells death. Our findings highlight a promising potential for LAVs, such as MMR, to be repurposed as cost-effective cancer immunotherapy.

immunology↗