# Measles Virus as an Oncolytic Immunotherapy **Authors:** Christine E. Engeland, Guy Ungerechts PMC · DOI: 10.3390/cancers13030544 · Cancers · 2021-02-01 ## TL;DR Measles virus is being studied as a cancer treatment that kills tumor cells and boosts the immune system's response against cancer. ## Contribution The paper highlights the use of genetically engineered measles virus as an oncolytic immunotherapy with potential for improved cancer treatment. ## Key findings - Measles virus selectively replicates in and kills cancer cells while activating antitumor immune responses. - Genetic engineering of measles virus allows for enhanced tumor targeting and therapeutic efficacy. - Early clinical trials show safety and promising efficacy of oncolytic measles virus in cancer treatment. ## Abstract Measles virus is currently under investigation as an innovative cancer treatment. The virus selectively replicates in and kills cancer cells. Furthermore, it can be genetically engineered to increase tumor specificity and therapeutic efficacy. Importantly, treatment with measles virus activates antitumor immune responses. A number of clinical trials using measles virus for cancer treatment have been completed or are ongoing. Future studies will further harness the possibilities of virus engineering and potential of combination immunotherapies to improve clinical outcome. Measles virus (MeV) preferentially replicates in malignant cells, leading to tumor lysis and priming of antitumor immunity. Live attenuated MeV vaccine strains are therefore under investigation as cancer therapeutics. The versatile MeV reverse genetics systems allows for engineering of advanced targeted, armed, and shielded oncolytic viral vectors. Therapeutic efficacy can further be enhanced by combination treatments. An emerging focus in this regard is combination immunotherapy, especially with immune checkpoint blockade. Despite challenges arising from antiviral immunity, availability of preclinical models, and GMP production, early clinical trials have demonstrated safety of oncolytic MeV and yielded promising efficacy data. Future clinical trials with engineered viruses, rational combination regimens, and comprehensive translational research programs will realize the potential of oncolytic immunotherapy. ## Linked entities - **Diseases:** cancer (MONDO:0004992) ## Full-text entities - **Genes:** Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1}, CD80 (CD80 molecule) [NCBI Gene 941] {aka B7, B7-1, B7.1, BB1, CD28LG, CD28LG1}, Cd3e (CD3 antigen, epsilon polypeptide) [NCBI Gene 12501] {aka CD3, CD3epsilon, T3e}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, NECTIN4 (nectin cell adhesion molecule 4) [NCBI Gene 81607] {aka EDSS1, LNIR, PRR4, PVRL4, nectin-4}, PNP (purine nucleoside phosphorylase) [NCBI Gene 4860] {aka NP, PRO1837, PUNP}, Ms4a1 (membrane-spanning 4-domains, subfamily A, member 1) [NCBI Gene 12482] {aka Cd20, Ly-44, Ms4a2}, HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, IFITM1 (interferon induced transmembrane protein 1) [NCBI Gene 8519] {aka 9-27, CD225, DSPA2a, IFI17, LEU13}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, CTNNBL1 (catenin beta like 1) [NCBI Gene 56259] {aka C20orf33, IMD99, NAP, P14L, PP8304, dJ633O20.1}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, Uprt (uracil phosphoribosyltransferase) [NCBI Gene 331487] {aka D830012I24Rik, Gm774}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, TNFSF10 (TNF superfamily member 10) [NCBI Gene 8743] {aka APO2L, Apo-2L, CD253, TANCR, TL2, TNLG6A}, Cd46 (CD46 antigen, complement regulatory protein) [NCBI Gene 17221] {aka Mcp}, Ctnnbl1 (catenin, beta like 1) [NCBI Gene 66642] {aka 5730471K09Rik, NAP, NYD-SP19, P14L}, EIF4E (eukaryotic translation initiation factor 4E) [NCBI Gene 1977] {aka AUTS19, CBP, EIF4E1, EIF4EL1, EIF4F, eIF-4E}, MIR31 (microRNA 31) [NCBI Gene 407035] {aka MIRN31, hsa-mir-31, miR-31}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, Ctla4 (cytotoxic T-lymphocyte-associated protein 4) [NCBI Gene 12477] {aka Cd152, Ctla-4, Ly-56}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, Cldn6 (claudin 6) [NCBI Gene 54419], SLC5A5 (solute carrier family 5 member 5) [NCBI Gene 6528] {aka NIS, TDH1}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, Igfbp2 (insulin-like growth factor binding protein 2) [NCBI Gene 16008] {aka IBP-2, Igfbp-2, mIGFBP-2}, RSAD2 (radical S-adenosyl methionine domain containing 2) [NCBI Gene 91543] {aka SAND, cig33, cig5, vig1}, Ifnar1 (interferon (alpha and beta) receptor 1) [NCBI Gene 15975] {aka Ifar, Ifnar, Ifrc, Infar}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, RIGI (RNA sensor RIG-I) [NCBI Gene 23586] {aka DDX58, RIG-I, RIG1, RLR-1, SGMRT2}, FOSL1 (FOS like 1, AP-1 transcription factor subunit) [NCBI Gene 8061] {aka FRA, FRA1, fra-1}, IFNB1 (interferon beta 1) [NCBI Gene 3456] {aka IFB, IFF, IFN-beta, IFNB}, IFIT1 (interferon induced protein with tetratricopeptide repeats 1) [NCBI Gene 3434] {aka C56, G10P1, IFI-56, IFI-56K, IFI56, IFIT-1}, IL15 (interleukin 15) [NCBI Gene 3600] {aka IL-15}, CD46 (CD46 molecule) [NCBI Gene 4179] {aka AHUS2, MCP, MIC10, TLX, TRA2.10}, Cxcl10 (C-X-C motif chemokine ligand 10) [NCBI Gene 15945] {aka C7, CRG-2, INP10, IP-10, IP10, Ifi10}, Ifnb1 (interferon beta 1, fibroblast) [NCBI Gene 15977] {aka IFN-beta, IFNB, If1da1, Ifb}, Cea (carcinoembryonic antigen gene family) [NCBI Gene 111518], Cd68 (CD68 antigen) [NCBI Gene 12514] {aka Lamp4, Scard1, gp110}, CGB5 (chorionic gonadotropin subunit beta 5) [NCBI Gene 93659] {aka CGB, HCG}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, Ifna (interferon alpha complex region) [NCBI Gene 111654] {aka Ifa, Ifa8}, CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, Slc5a5 (solute carrier family 5 (sodium iodide symporter), member 5) [NCBI Gene 114479] {aka NIS}, Dct (dopachrome tautomerase) [NCBI Gene 13190] {aka DT, TRP-2, TRP2, Tyrp-2, Tyrp2, slaty}, HSP90AA1 (heat shock protein 90 alpha family class A member 1) [NCBI Gene 3320] {aka EL52, HEL-S-65p, HSP86, HSP89A, HSP90A, HSP90N}, IFNAR1 (interferon alpha and beta receptor subunit 1) [NCBI Gene 3454] {aka AVP, CRF2-1, IFN-R-1, IFN-alpha-REC, IFNAR, IFNBR}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, SLAMF1 (signaling lymphocytic activation molecule family member 1) [NCBI Gene 6504] {aka CD150, CDw150, IPO3, SLAM}, MS4A1 (membrane spanning 4-domains A1) [NCBI Gene 931] {aka B1, Bp35, CD20, CVID5, FMC7, LEU-16}, Csf2 (colony stimulating factor 2 (granulocyte-macrophage)) [NCBI Gene 12981] {aka CSF, Csfgm, GMCSF, Gm-CSf, MGI-IGM}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PLAU (plasminogen activator, urokinase) [NCBI Gene 5328] {aka ATF, BDPLT5, QPD, UPA, URK, u-PA}, FURIN (furin, paired basic amino acid cleaving enzyme) [NCBI Gene 5045] {aka FUR, PACE, PCSK3, SPC1} - **Diseases:** adult T cell leukemia/lymphoma (MESH:D015459), B cell lymphomas (MESH:D016393), cutaneous T cell lymphoma (MESH:D016410), melanoma (MESH:D008545), carcinomas of pancreatic, colorectal, and mammary origin (MESH:D015179), glioma (MESH:D005910), Burkitt's lymphoma (MESH:D002051), TAA (MESH:D017545), malignant peripheral nerve sheath tumors (MESH:D018319), infection (MESH:D007239), tumor-associated antigen (MESH:C535887), skin rash (MESH:D005076), prostate cancer (MESH:D011471), multiple myeloma (MESH:D009101), hepatocellular carcinoma (MESH:D006528), mass (MESH:C536030), pleural effusion (MESH:D010996), Lymphoma (MESH:D008223), ovarian cancer (MESH:D010051), glioblastoma (MESH:D005909), EBV- (MESH:D020031), mesothelioma (MESH:D008654), infectious disease (MESH:D003141), bladder cancer (MESH:D001749), medulloblastoma (MESH:D008527), pancreatic adenocarcinoma (MESH:D010190), Cancer (MESH:D009369), hematological malignancies (MESH:D019337), laryngeal cancer (MESH:D007822), colorectal adenocarcinoma (MESH:D003110), breast cancer (MESH:D001943), head and neck squamous cell carcinoma (MESH:D000077195), MeV (MESH:D008457) - **Chemicals:** 2-fluoroadenine (MESH:C038208), lipid (MESH:D008055), gemcitabine (MESH:D000093542), graphene oxide (MESH:C000628730), cyclophosphamide (MESH:D003520), TAA (MESH:D013853), camptothecin (MESH:D002166), Edmonston-Zagreb measles vaccine (-), dichloroacetate (MESH:D003999), 5-FC (MESH:D005437), polyinosinic acid (MESH:D011069), ruxolitinib (MESH:C540383), paclitaxel (MESH:D017239), 6-methylpurine-2'-deoxyriboside (MESH:C032885), B (MESH:D001895), 123I (MESH:C000614958), fludarabine (MESH:C024352), 6-methylpurine (MESH:C016588), COO (MESH:C041069), nimotuzumab (MESH:C501466), polymers (MESH:D011108), 5-FU (MESH:D005472), 99m-technetium (MESH:D013667) - **Species:** Mus musculus (house mouse, species) [taxon 10090], mumps virus [taxon 1979165], canine distemper virus [taxon 11232], Measles morbillivirus (no rank) [taxon 11234], Morbillivirus (genus) [taxon 11229], Macaca mulatta (rhesus macaque, species) [taxon 9544], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606], Saimiri (squirrel monkeys, genus) [taxon 9520], Helicobacter pylori (species) [taxon 210] - **Mutations:** N481Y - **Cell lines:** MC38 — Mus musculus (Mouse), Mouse colon adenocarcinoma, Cancer cell line (CVCL_B288), B16 — Mus musculus (Mouse), Hybridoma (CVCL_U043), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), MV-NIS — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_6005), MC38cea — Mus musculus (Mouse), Mouse colon adenocarcinoma, Cancer cell line (CVCL_5I36), MV — Homo sapiens (Human), Transformed cell line (CVCL_0541), B16 melanoma — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_F936), T3M4 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_4056), KM12 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_1331) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC7867054/full.md ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC7867054/full.md ## References 155 references — full list in the complete paper: https://tomesphere.com/paper/PMC7867054/full.md --- Source: https://tomesphere.com/paper/PMC7867054