{"entity":{"id":"paper-martuza-engineered-hsv-glioma-science-1991","kind":"paper","name":"Martuza 1991: the first genetically engineered virus built to treat a cancer","aka":[],"tldr":"A herpes virus was deliberately crippled so that it could only multiply in dividing cells, injected into human brain tumours growing in mice, and it made the mice live longer.","summary":"Malignant gliomas are the commonest malignant brain tumours and are almost always fatal. Martuza and colleagues tested dlsptk, a thymidine-kinase-negative mutant of herpes simplex virus type 1 attenuated for neurovirulence, as a treatment. In cell culture it killed two long-term human glioma lines and three short-term human glioma cell populations. In nude mice with implanted subcutaneous and subrenal U87 human gliomas, injection into the tumour inhibited growth; in mice with intracranial U87 gliomas it prolonged survival.\n\nDeleting viral thymidine kinase makes the virus depend on the host cell's own nucleotide pool, which dividing tumour cells supply and resting brain cells do not. That is the first worked example of the move the whole field now makes: take out a viral gene whose job the cancer cell will do for it.","asOf":"2026-09-25","links":[{"label":"Science 1991","url":"https://doi.org/10.1126/science.1851332"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/1851332/"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["robert-martuza"],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":1991,"doi":"10.1126/science.1851332","pmid":"1851332","authors":"Martuza RL, Malick A, Markert JM, Ruffner KL, Coen DM","paperType":"basic","findings":["A thymidine-kinase-negative herpes simplex virus type 1 mutant (dlsptk), attenuated for neurovirulence, killed two long-term and three short-term human glioma cell populations in culture.","Injection into subcutaneous and subrenal U87 human gliomas in nude mice inhibited tumour growth.","Injection into intracranial U87 gliomas in nude mice prolonged survival."],"whatItMeans":"This paper turned oncolytic virotherapy from a century of case reports into an engineering discipline. Every approved product descends from the same idea: delete a viral gene that a normal cell would have to supply and a cancer cell already supplies in excess. Talimogene laherparepvec and teserpaturev are both herpes viruses in this line.","caveats":["Thymidine kinase deletion also removes the virus's sensitivity to aciclovir and ganciclovir, which are the safety net if an infection runs away. Later constructs deleted different genes partly for that reason.","Nude mice have no T cells, so the experiment measures direct lysis only.","A human glioma grown in a mouse flank or brain is a poor model of the infiltrating disease in a patient, and three decades later glioblastoma remains almost as lethal."]},"route":"/key-papers/paper-martuza-engineered-hsv-glioma-science-1991/","neighbours":{"cancer":[{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"section":[{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}],"person":[{"id":"robert-martuza","kind":"person","name":"Robert L. Martuza","route":"/people/robert-martuza/"}],"journal":[{"id":"science","kind":"journal","name":"Science","route":"/journals/science/"}]}}