Squamous cell cancer of the head and neck (SCCHN) is locally invasive, and frequently spreads to the cervical lymph nodes. Locally advanced disease is treated with radiotherapy plus chemotherapy and/or cetuximab (an anti-EGF receptor antibody), but the cure rate is less than 40% and toxicities are severe. The overall goal of this SBIR grant proposal is to enhance the outcomes of therapy for patients with locally advanced or relapsed SCCHN without increasing treatment related toxicity. MV-NIS is an improved oncolytic measles virus that has been engineered to code for the thyroidal sodium iodide symporter (NIS), is amenable to noninvasive monitoring by radioiodine imaging and has antitumor activity in the FaDu mouse xenograft model of human SCCHN. MV-NIS has been administered safely to human subjects but never by direct intratumoral injection. In light of its demonstrated safety, its activity in preclinical SCCHN models, and its potential compatibility with chemoradiotherapy, we now hypothesize that MV-NIS can significantly enhance the outcomes of therapy for SCCHN when correctly incorporated into existing treatment programs for locally advanced disease. Specific aims are as follows: Phase I SBIR Aim 1. To evaluate the impact of humoral immunity on the antitumor activity of MV-NIS, given as direct intratumoral injection, in mice with human SCCHN xenografts. Phase II SBIR Aim 2. To conduct a phase I clinical trial of single agent MV-NIS, administered by intratumoral inoculation, in patients with relapsed SCCHN. Aim 3. To determine whether established treatment modalities for SCCHN are compatible with intratumoral MV-NIS in preclinical models. Upon completion of this work, NISCO will be ready to combine MV-NIS with conventional SCCHN frontline therapy in a phase II clinical trial in patients with locally advanced disease. This will be the precursor of a pivotal phase II/III study to prove the utility of MV-NIS in the treatment of locally advanced SCCHN. , ,
Public Health Relevance: Oncolytic virotherapy is a promising new approach to the treatment of cancer, but its development has been hindered by the lack of available technologies for non-invasively monitoring the spread and elimination of the virus infection in a treated patient. NISCO has acquired an oncolytic measles virus (MV-NIS) that has been engineered to facilitate the application of non-invasive imaging technologies to monitor its spread. Based on the observation that MV-NIS is effective in a preclinical model of head and neck cancer, NISCO now proposes to advance the virus to clinical testing in poor prognosis patients with this form of cancer. The expectation is that the new virus will prove effective therapy for head and neck cancer and that non-invasive monitoring of viral spread will allow us to optimize dosing, scheduling, and synergistic interactions with conventional head and neck cancer treatments.
Thesaurus Terms: (Sp-4-2)-Diamminedichloroplatinum;131 Iodine;2,4-Dioxo-5-Fluoropyrimidine;2h-1,3,2-Oxazaphosphorin-2-Amine, N,N-Bis(2-Chloroethyl)Tetrahydro-, 2-Oxide;2h-1,3,2-Oxazaphosphorin-2-Amine, N,N-Is(2-Chloroethyl)Tetrahydro-,2-Oxide;5-Fu;5-Fluoro-2,4(1h,3h)-Pyrimidinedione;5-Fluorouracil;5-Fluracil;5fu;Agreement;Anti-Egfr Monoclonal Antibody;Anti-Epidermal Growth Factor Receptor Monoclonal Antibody;Antibodies;Applications Grants;Athymic Nude Mouse;Buccal Cavity;Cddp;Ctx;Cyclo-Cell;Cancer Radiotherapy;Cancer Treatment;Cancer Of The Ovary;Cancers;Carloxan;Cavitas Oris;Cells;Cervical Lymph Node;Cervical Lymph Node Group;Cetuximab;Ciclofosfamida;Ciclofosfamide;Cicloxal;Cis-Diammine-Dichloroplatinum;Cis-Diamminedichloridoplatinum;Cis-Diamminedichloro Platinum (Ii);Cis-Dichloroammine Platinum (Ii);Cis-Platinous Diamine Dichloride;Cis-Platinum Ii;Cis-Platinum Ii Diamine Dichloride;Cisplatin;Cisplatina;Cisplatinum;Clafen;Claphene;Clinic;Clinical;Clinical Evaluation;Clinical Research;Clinical Study;Clinical Testing;Clinical Trials;Clinical Trials, Phase I;Clinical Trials, Phase Ii;Clinical Trials, Unspecified;Code;Coding System;Cycloblastin;Cycloblastine;Cyclophospham;Cyclophosphamide;Cyclophosphamidum;Cyclophosphan;Cyclophosphane;Cyclophosphanum;Cyclostin;Cyclostine;Cysplatyna;Cytophosphan;Cytophosphane;Cytoxan;Ddp;Data;Development;Dichlorodiammineplatinum;Dose;Drugs, Non-Prescription;Drugs, Nonprescription;Egfr;Erbb Protein;Erbb1;Early-Stage Clinical Trials;Endoxan;Endoxana;Enduxan;Engineering;Engineerings;Epidermal Growth Factor Receptor;Epidermal Growth Factor Receptor Kinase;Epidermal Growth Factor Receptor Protein-Tyrosine Kinase;Epidermoid Cell Cancer;Epithelial;Exposure To;Fluoro Uracil;Fluorouracil;Fluoruracil;Fluouracil;Forecast Of Outcome;Fosfaseron;Future;Gene Expression;Gene Transfer;Genoxal;Genuxal;Giant Cells;Goals;Grant Proposals;Grants, Applications;Her1;Hnscc;Head And Neck;Head And Neck Cancer;Head And Neck Carcinoma;Head And Neck Neoplasm (Excluding Central Nervous System);Head And Neck Neoplasms;Head And Neck Squamous Cell Carcinoma;Head And Neck, Buccal Cavity;Head And Neck, Pharynx;Head And Neck Structure;Heterograft;Human;Human Cell Line;Human, General;Humoral Immunities;I-131;I131 Isotope;Iv Drip;Image;Imaging Technology;Immune;Immunities, Humoral;In Vitro;Injection Of Therapeutic Agent;Injections;Intravenous Drip;Intravenous Infusion;Iodine I 131;Isotopes;Killings;Kinetic;Kinetics;Ledoxina;Licensing;Life;Light;Malignant Epidermoid Cell Neoplasm;Malignant Epidermoid Cell Tumor;Malignant Head And Neck Neoplasm;Malignant Neoplasm Therapy;Malignant Neoplasm Treatment;Malignant Neoplasms;Malignant Ovarian Neoplasm;Malignant Ovarian Tumor;Malignant Squamous Cell Neoplasm;Malignant Squamous Cell Tumor;Malignant Tumor;Malignant Tumor Of The Head And Neck;Malignant Tumor Of The Ovary;Malignant Neoplasm Of Ovary;Mammals, Mice;Man (Taxonomy);Man, Modern;Measles;Measles Virus;Mediating;Mediation;Mice;Mice, Athymic;Mice, Nude;Mitoxan;Modality;Modeling;Monitor;Mouth;Multinucleated Giant Cells;Multiple Myeloma;Murine;Mus;Myeloma, Plasma-Cell;Ndul;Nis Gene;Nis Protein;Na(+),I(-)-Cotransporter;Negotiating;Negotiation;Neosar;Nodule;Non-Prescription Drugs;Nude Mice;Otc Drugs;Oncolytic;Oral Cavity;Over-The-Counter Drugs;Patent Medicines;Patients;Peyrone's Chloride;Peyrone's Salt;Pharyngeal Structure;Pharynx;Pharynxs;Phase;Phase 1 Clinical Trials;Phase 2 Clinical Trials;Phase I Clinical Trials;Phase I Study;Phase Ii Clinical Trials;Photoradiation;Platinum Diamminodichloride;Platinum, Diaminedichloro-, Cis- (8ci);Platinum, Diamminedichloro-, (Sp-4-2)-;Polykaryocytes;Pre-Clinical Model;Preclinical Models;Procytox;Prognosis;Radiation Therapy;Radiotherapeutics;Radiotherapy;Receptor, Egf;Receptor, Tgf-Alpha;Receptor, Urogastrone;Receptors, Epidermal Growth Factor-Urogastrone;Recombinants;Refractory;Regional Lymph Node Involvement;Relapse;Rubeola;Sbir;Sbirs (R43/44);Scchn;Sched;Slc5a5;Slc5a5 Gene;Safety;Schedule;Sendoxan;Site;Skin;Small Business Innovation Research;Small Business Innovation Research Grant;Sodium-Iodide Symporter Gene;Speed;Speed (Motion);Squamous Cell Cancers;Surface;Syklofosfamid;Syncytium;Tc 99m;Technetium 99m;Technology;Throat;Toxic Effect;Toxicities;Transforming Growth Factor Alpha Receptor;Transplantation, Heterologous;Tumor Cell;Tumor Of The Head And Neck;Validation;Viral;Viral Diseases;Viral Genes;Virus;Virus Diseases;Viruses, General;Work;Xenograft;Xenograft Model;Xenograft Procedure;Xenotransplantation;Zytoxan;Advanced Disease;Anti-Cancer Therapeutic;Antibody-Based Immunity;Anticancer Therapeutic;Anticancer Therapy;Attenuated Measles Virus;Base;C-Erbb-1;C-Erbb-1 Protein;Cancer Therapy;Cell Killing;Chemotherapy;Cis Dichlorodiammineplatinum;Cis Platinum Compound;Cis-Diaminedichloroplatinum;Cis-Diamminedichloroplatinum;Cis-Diamminedichloroplatinum(Ii);Cis-Dichlorodiammineplatinum(Ii);Cis-Platinum;Clinical Investigation;Clinical Test;College;Drip Infusion;Effective Therapy;Erbb-1;Erbb-1 Proto-Oncogene Protein;Erbbl;Expectation;Head & Neck Cancer;Head & Neck Tumor;Head And Neck Tumor;Human Subject;Imaging;Improved;In Vivo;Innovate;Innovation;Innovative;Intraperitoneal;Intravenous Administration;Irradiation;Malignancy;Morbilli;Myeloma;Myelomatosis;Neoplasm/Cancer;Neoplastic Cell;New Approaches;Non-Invasive Monitor;Novel Approaches;Novel Strategies;Novel Strategy;Oncolysis;Outcome Forecast;Ovarian Cancer;Phase 1 Study;Phase 1 Trial;Phase 2 Study;Phase 2 Trial;Phase I Trial;Phase Ii Trial;Pre-Clinical;Preclinical;Proto-Oncogene Protein C-Erbb-1;Protocol, Phase I;Protocol, Phase Ii;Public Health Relevance;Radiolabel;Radiotracer;Research Clinical Testing;Rougeole Virus;Rubeola Virus;Sodium-Iodide Cotransporter;Sodium-Iodide Symporter;Study, Phase Ii;Therapy Outcome;Thyroid Iodide Transporter;Transfer Of A Gene;Treatment Program;Tumor;Tumor Growth;Tumor Xenograft;Vein Infusion;Viral Infection;Virus Infection
