Index

Note: Page numbers of article titles are in boldface type

A

Ablative gene therapy. See Suicide genes.

Ad-p53. See Adenoviruses.

Adeno-associated virus, as a vector forcancer gene therapy, 510–511

Adenoviruses, Ad-p53 gene therapy for lungcancer, 521–535

clinical trials with p53 genetransfer, 523–526and chemotherapy, 526–527and radiation therapy,

528–530future trials, 530–533molecular role of p53 in lung

cancer, 521–523as vectors for cancer gene therapy,

507–508in head and neck cancer, 591–592

oncolytic, basic viral biology of, 663clinical studies with, 673–674in ‘‘gene therapy’’ for head and

neck cancer, 598–599p53-targeted, liver-directed viral

therapy for cancer using, 571–588objectives of studies of, 574–575results of studies of, 575–580therapeutic adenoviruses,

573–574dl1520 (Onyx-015), 573–574SCH 58500 (vAd.p53), 574

Adoptive cellular therapy, applications ofgene transfer, 621–643

dendritic cells, 635–637gene delivery using nonviral

vectors, 622–623gene delivery using viral vectors,

621–622generation of tumor-reactive

T cells using geneticallymodified tumors, 623–629effector cells, 627–629tumor-infiltrating lympho-

cytes, 624–627genetic modification of effector

T cells, 629–632redirection of effector

T cells with chimericreceptor genes,631–632

tumor-infiltrating lympho-cytes transduced toproduce cytokines,629–631

genetic modification of naivecells, 632–634

stem cells, 634–635

Allogeneic tumor cell lines, genetransfer-based immunotherapeuticapproaches to pancreatic cancer using,542–543

Angioendothelioma, approved cancer genetherapy trials in, 825

Antiangiogenic gene therapy, for pancreaticcancer, 548–549

Antigens, tumor, identification of, 685–686in pancreatic cancer, and gene

transfer-based immunotherapyfor, 545–548

Antioncogene gene therapy, in head andneck cancer, 598

Antisense oncogenes, in cancer genetherapy, 499–500

Arterial delivery, of liver-directed viraltherapy for cancer, using hepaticarterial infusion, 571–588

Autologous tumor cells, gene transfer-based immunotherapeutic approachesto pancreatic cancer using, 539,541–542

B

Biological vectors, for cancer gene therapy,511

Bladder cancer, approved cancer genetherapy trials in, 804

Surg Oncol Clin N Am

11 (2002) 827–834

1055-3207/02/$ - see front matter � 2002, Elsevier Science (USA). All rights reserved.

PII: S 1 0 5 5 - 3 2 0 7 ( 0 2 ) 0 0 0 7 4 - 1

Bone marrow protection, in gene transfertherapy for pancreatic cancer, 549–550

Brain tumors, approved cancer genetherapy trials in, 740–753

Breast cancer, approved cancer genetherapy trials in, 753–759

Bystander cells, universal, gene transfer-based immunotherapeutic approachesto pancreatic cancer using, 542–543

Bystander effects, in gene therapy of headand neck cancer, 600

C

Cancer gene therapy. See Gene therapy,for cancer.

Carcinoembryonic antigen (CEA),approved cancer gene therapy trials inCEA-positive malignancies, 759–763in pancreatic cancer, and gene

transfer-based immunotherapyfor, 545–546

Cellular immunotherapy. See Adoptivecellular therapy.

Cervical cancer, approved cancer genetherapy trials in, 798

Chemotherapy, in conjunction withgenetically modified tumor vaccines,691–692with p53 gene transfer, in lung cancer,

526–527

Chimeric receptor genes, redirectionof effector T cells with, 631–632

Chimeric T-cell receptors, gene transfer-based immunotherapeutic approachesto pancreatic cancer using, 544

Clinical trials, for cancer gene therapy(Appendix), 717–825

Colon cancer, approved cancer genetherapy trials in, 772–774

Colorectal cancer, approved cancer genetherapy trials in, 774–775liver metastases, viral therapy with

p53-targeted adenoviruses,571–588objectives of studies of, 574–575results of studies of, 575–580therapeutic adenoviruses,

573–574dl1520 (Onyx-015), 573–574SCH 58500 (vAd.p53), 574

Corrective gene therapy, for prostatecancer, 612–614

Cytokine-modified tumor vaccines, 681–696in cancer gene therapy, future

directions, 692–693identifying tumor-specific

antigens, 685–687incorporating into other treat-

ment modalities, 691–692results with, in clinical trials,

687–691role for immune system in tumor

rejection, 682–685

Cytokines, tumor-infiltrating lymphocytestransduced to produce, 629–631

D

Dendritic cell gene therapy, 645–660

Dendritic cells, gene therapy with, 645–660nucleic acids, 653–655other methods, 655peptides, 649–653physiology, 647–648vaccine development, 648–649

gene transfer-based immuno-therapeutic approaches topancreatic cancer using, 543–544

in adoptive cellular therapy, 635–637

dl1520 (Onyx-015) adenovirus, liver-directed viral therapy for cancer using,573–574, 575, 577, 579–584

DNA-binding component, in protein/DNApolyplexes, for cancer gene therapy,698–703

DNA/protein polyplexes. See Protein/DNApolyplexes.

E

Effector cells, generation of from lymphnodes draining genetically modifiedtumors, 627–629genetic modification of, 629–632

Endosomal lysis agents, in protein/DNApolyplexes, for cancer gene therapy,705–707

Epidermal growth factor, in pancreaticcancer, and gene transfer-basedimmunotherapy for, 546

Epidermal growth factor receptor, inpancreatic cancer, and gene transfer-based immunotherapy for, 546

828 Index / Surg Oncol Clin N Am 11 (2002) 827–834

Episomal replication, in protein/DNApolyplexes, for cancer gene therapy,707–708

G

Gastrointestinal malignancies, approvedcancer gene therapy trials in, 772–779

Gene therapy, for cancer, 497–825applications of gene transfer to cellular

immunotherapy, 621–643dendritic cells, 635–637gene delivery using nonviral

vectors, 622–623gene delivery using viral vectors,

621–622generation of tumor-reactive

T cells using geneticallymodified tumors, 623–629effector cells, 627–629tumor-infiltrating lympho-

cytes, 624–627genetic modification of effector

T cells, 629–632redirection of effector

T cells with chimericreceptor genes,631–632

tumor-infiltrating lympho-cytes transduced toproduce cytokines,629–631

genetic modification of naivecells, 632–634

stem cells, 634–635clinical trials for (Appendix), 717–825

breast cancer, 753–759CEA-positive malignancies,

759–763gastrointestinal malignancies,

772–779gynecologic cancers, 798–804head and neck cancer, 779–789hematologic malignancies,

763–772lung cancer, 790–798melanoma, 718–738miscellaneous, 825nervous system tumors, 738–753solid tumors, 822–824urologic cancers, 804–822

cytokine-modified tumor vaccines,681–696future directions, 692–693identifying tumor-specific

antigens, 685–687incorporating into other treat-

ment modalities, 691–692

results with, in clinical trials,687–691

role for immune system in tumorrejection, 682–685

dendritic cell, 645–660nucleic acids, 653–655other methods, 655peptides, 649–653physiology, 647–648vaccine development, 648–649

for head and neck cancer, 589–606antioncogene, 598enhancing efficiency and

specificity of, 599–600bystander effects, 600vector targeting, 599–600

foreseeable applications of,601–602

immunologic, 596–598oncolytic adenovirus ‘‘gene

therapy,’’ 598–599vectors, 590–592with suicide genes, 595–596with tumor suppressor genes, 593

p16 and p21, 595p53, 593–595

for liver metastases of colorectalcancer, with p53-targetedadenoviruses, 571–588objectives of studies of, 574–575replication-selective virology,

584–585results of studies of, 575–580therapeutic adenoviruses,

573–574dl1520 (Onyx-015), 573–574SCH 58500 (vAd.p53), 574

for lung cancer, Ad-p53 therapy,521–535clinical trials with p53 gene

transfer, 523–530future trials, 530–533molecular role of p53 in lung

cancer, 521–523for pancreatic cancer, 537–569

strategies requiring efficienttransduction, 550–553oncogene targeting, 550prodrug activation

or selective viralreplication, 552–553

tumor suppressor replace-ment, 551–552

strategies requiring limited trans-duction, antiangiogenicgene therapy, 548–549bone marrow protection,

549–550immunotherapies, 539–548

829Index / Surg Oncol Clin N Am 11 (2002) 827–834

Gene therapy (continued )for prostate cancer, 607–620

ablative or suicide genes, 614–617combination of approaches, 617corrective, 612–614immunotherapy, 608–612

introduction to, 497–519strategies for, 499–505

gene modification of im-mune effector cells, 503

genetically modified tumorvaccines, 503–505

oncolytic viruses, 502–503prodrug activation of

‘‘suicide’’ genetherapy, 501–502

transcriptional targeting,500–501

tumor suppressor genes andantisense oncogenes,499–500

vector systems for, 505–512adeno-associated virus,

510–511adenovirus, 507–508herpes simplex virus,

508–509nonviral gene delivery

systems, 511–512retrovirus, 505–507vaccinia virus, 509–510

protein/DNA polyplexes for,697–716cell targeting ligands, 703–705DNA-binding components,

698–703endosomal lysis agents, from

viruses to polycations,705–707

future directions, 712–713molecular conjugates versus viral

and nonviral vectors,710–712

nuclear translocation, episomalreplication, and integration,707–708

nucleic acids, from oligonucleo-tides to plasmids, 708–710

viral oncolysis, 661–680

Genetically modified tumor vaccines.See Cytokine-modified vaccines.

Genetically modified tumors. See Adoptivecellular therapy.

Glioblastoma, approved cancer genetherapy trials in, 742–746

Glioma, approved cancer gene therapy trialsin, 746–749

Granulocyte-macrophage colony-stimulating factor (GM-CSF),GM-CSF-secreting tumor vaccines,688–690

Gynecologic cancers, approved cancer genetherapy trials in, 799–805

H

Head and neck cancer, approved cancergene therapy trials in, 779–790gene therapy for, 589–606

antioncogene, 598enhancing efficiency and specifi-

city of, 599–600bystander effects, 600vector targeting, 599–600

foreseeable applications of,601–602

immunologic, 596–598nonviral vectors for, 592oncolytic adenovirus, 598–599viral vectors for, 591–592with suicide genes, 595–596with tumor suppressor genes, 593

p16 and p-21, 595p53, 593–595

Hematologic malignancies, approved cancergene therapy trials in, 763–772

Hepatic arterial infusion, of liver-directedviral therapy for cancer, 571–588

Hepatocellular carcinoma, approved cancergene therapy trials in, 772

Herpes simplex virus, as a vector for cancergene therapy, 508–509oncolytic, basic viral biology of, 663

clinical studies with, 674–675

I

Immune effector cells, gene modification of,in cancer gene therapy, 503

Immunologic gene therapy.See Immunotherapeutic approaches.

Immunotherapeutic approaches, to genetherapy, applications of genetransfer to cellular immunotherapy,621–643

dendritic cells, 635–637gene delivery using nonviral

vectors, 622–623gene delivery using viral vectors,

621–622

830 Index / Surg Oncol Clin N Am 11 (2002) 827–834

generation of tumor-reactiveT cells using geneticallymodified tumors, 623–629effector cells, 627–629tumor-infiltrating lympho-

cytes, 624–627genetic modification of effector

T cells, 629–632redirection of effector

T cells with chimericreceptor genes,631–632

tumor-infiltrating lympho-cytes transduced toproduce cytokines,629–631

genetic modification of naivecells, 632–634

stem cells, 634–635cytokine-modified tumor vaccines,

681–696future directions, 692–693identifying tumor-specific

antigens, 685–687incorporating into other treat-

ment modalities, 691–692results with, in clinical trials,

687–691role for immune system in tumor

rejection, 682–685for head and neck cancer, 596–598for pancreatic cancer, 537–569

allogeneic tumor cell lines and‘‘universal bystander’’ cells,542–543

autologous tumor cells, 539,541–542

chimeric T-cell receptors, 544dendritic cells, 543–544genes used in, 544–548

for prostate cancer, 608–612ablative or suicide genes, 614–617combination of approaches, 617corrective, 612–614

K

K-ras, in pancreatic cancer, and genetransfer-based immunotherapyfor, 545

L

Leukemia, approved cancer gene therapytrials in, 763–769

Ligands, cell targeting, in protein/DNApolyplexes, for cancer gene therapy,703–705

Liposomal vectors, for cancer gene therapy,511–512

in head and neck cancer, 592

Liver metastases, from colorectal cancer,approved cancer gene therapy trialsin, 776–778from colorectal cancer, viral therapy

with p53-targeted adenoviruses,571–588objectives of studies of, 574–575results of studies of, 575–580therapeutic adenoviruses,

573–574dl1520 (Onyx-015), 573–574SCH 58500 (vAd.p53), 574

Lung cancer, Ad-p53 gene therapy for,521–535

clinical trials with p53 genetransfer, 523–526and chemotherapy, 526–527and radiation therapy,

528–530future trials, 530–533molecular role of p53 in, 521–523

approved cancer gene therapy trialsin, 791–799

Lymph nodes, tumor-draining, generationof effector cells from geneticallymodified tumors, 627–629

Lymphocytes, tumor-infiltrating (TIL),generation of from geneticallymodified tumors, 624–627genetic modification of, transduced

to produce cytokines, 629–632

Lymphoma, approved cancer gene therapytrials in, 769–771

M

Melanoma, approved cancer gene therapytrials in, 718–738

Mesothelioma, approved cancer genetherapy trials in, 797–798

Metastases, liver, from colorectal cancer,approved cancer gene therapy trials in,776–778

viral therapy with p53-targetedadenoviruses, 571–588dl1520 (Onyx-015), 573–574objectives of studies of,

574–575results of studies of,

575–580SCH 58500 (vAd.p53), 574

831Index / Surg Oncol Clin N Am 11 (2002) 827–834

Metastases (continued )therapeutic adenoviruses,

573–574

MUC-1, in pancreatic cancer, and genetransfer-based immunotherapy for, 546

N

National Institutes of Health, RecombinantAdvisory Committee, clinical trials forcancer gene therapy approved by,717–825

Neck, cancer of. See Head and neck cancer.

Nervous system tumors, approved cancergene therapy trials in, 738–753

Neuroblastoma, approved cancer genetherapy trials in, 749–753

Newcastle disease virus, oncolytic, basicviral biology of, 664

clinical studies with, 675–676

Nuclear translocation, in protein/DNApolyplexes, for cancer gene therapy,707–708

Nucleic acids, in cancer gene therapy withdendritic cells, 653–655in protein/DNA polyplexes, for cancer

gene therapy, 708–710

O

Oncogenes, antisense, in cancer genetherapy, 499–500inhibition of, in gene transfer therapy

for pancreatic cancer, 550

Oncolysis, viral. See Oncolytic viruses.

Oncolytic adenoviruses, in ‘‘gene therapy’’for head and neck cancer, 598–599

Oncolytic viruses, in cancer gene therapy,502–503, 661–680

basic viral biology, 663–664adenovirus, 663herpes simplex virus, 663Newcastle disease virus, 664reovirus, 664vaccinia virus, 664

clinical studies, 671–676adenovirus, 673–674herpes simplex virus,

674–675Newcastle disease virus,

675–676vaccinia virus, 675

historical background, 661–663preclinical studies, 664–671

optimizing antitumorefficacy, 668–671

optimizing tumor-specificreplication, 664–668

Onyx-015 (dl1520) adenovirus,liver-directed viral therapy for cancerusing, 573–574, 575, 577, 579–584

Ovarian cancer, approved cancer genetherapy trials in, 798–804

P

p16, in tumor suppressor gene therapyof head and neck cancer, 595

p21, in tumor suppressor gene therapyof head and neck cancer, 595

p53, Ad-p53 gene therapy for lung cancer,521–535

clinical trials with p53 genetransfer, 523–526and chemotherapy, 526–527and radiation therapy,

528–530future trials, 530–533molecular role of p53 in lung

cancer, 521–523in tumor suppressor gene therapy

of head and neck cancer,593–595

liver-directed viral therapy for cancerwith p53-targeted adenoviruses,571–588

Pancreatic cancer, approved cancer genetherapy trials in, 779gene therapy for, 537–569

strategies requiring efficienttransduction of cells,550–553oncogene targeting, 550prodrug activation or selec-

tive viral replication,552–553

tumor suppressor replace-ment, 551–552

strategies requiring limited trans-duction of cells, 539–550antiangiogenic gene

therapy, 548–549bone marrow protection,

549–550immunotherapies, 539–548

Peptides, pulsing dendritic cells with,in cancer gene therapy, 649–653

832 Index / Surg Oncol Clin N Am 11 (2002) 827–834

Polycations, endosomal lysis agents inprotein/DNA polyplexes, for cancergene therapy, 705–707

Prodrug activation, in cancer gene therapy,501–502

for pancreatic cancer, 552

Prostate cancer, approved cancer genetherapy trials in, 805–819gene therapy for, 607–620

ablative or suicide genes, 614–617combination of approaches, 617corrective, 612–614immunotherapy, 608–612

Protein/DNA polyplexes, for cancer genetherapy, 512, 697–716

cell targeting ligands, 703–705DNA-binding components,

698–703endosomal lysis agents, from

viruses to polycations,705–707

future directions, 712–713molecular conjugates versus viral

and nonviral vectors,710–712

nuclear translocation, episomalreplication, and integration,707–708

nucleic acids, from oligonucleo-tides to plasmids, 708–710

PTEN, in pancreatic cancer, and genetransfer-based immunotherapy for,546–547

R

Radiation therapy, with p53 gene transfer,in lung cancer, 528–530

Renal cancer, approved cancer gene therapytrials in, 819–822

Replication, viral, selective, in gene therapyof pancreatic cancer, 552–553

Replication-selective virology, 584–585

Retroviruses, as vectors for cancer genetherapy, 505–507

S

SCH 58500 (vAd.p53) adenovirus,liver-directed viral therapy for cancerusing, 574, 575–584

Skin metastases, approved cancer genetherapy trials in, 825

Soft tissue sarcoma, approved cancer genetherapy trials in, 825

Solid tumors, approved cancer gene therapytrials in, 822–825

Squamous cell carcinoma, of head and neck.See Head and neck cancer.

Stem cells, in adoptive cellular therapy,634–635

Suicide genes, in cancer gene therapy,501–502

head and neck cancer, 595–596prostate cancer, 614–617

T

T cells, genetic modification of effector,629–632

redirection of, with chimericreceptor genes, 631–632

tumor-infiltrating lymphocytestransduced to producecytokines, 629–631

genetic modification of naive, 632–633tumor-reactive, generation of using

genetically modified tumors,623–629effector cells, 627–629tumor-infiltrating lymphocytes,

624–627

T-cell receptors, chimeric, gene transfer-based immunotherapeutic approachesto pancreatic cancer using, 544

Testicular germ cell cancer, approved cancergene therapy trials in, 822

Transcriptional targeting, in cancer genetherapy, 500–501

Trials. See Clinical trials.

Tumor antigens, in pancreatic cancer, andgene transfer-based immunotherapyfor, 545–548

Tumor suppressor genes, in cancer genetherapy, 499–500

in head and neck cancer, 593p16 and p21, 595p53, 593–595

in pancreatic cancer, restorationof function, 551–552

Tumor vaccines, cytokine-modified,681–696

Tumor-draining lymph nodes, generationof effector cells from geneticallymodified tumors, 627–629

Tumor-infiltrating lymphocytes (TIL),generation of from geneticallymodified tumors, 624–627

833Index / Surg Oncol Clin N Am 11 (2002) 827–834

Tumor-infiltrating (continued )genetic modification of, transduced

to produce cytokines, 629–632

Tumors, genetically modified, generation oftumor-reactive T cells using, 623–629

effector cells derived from lymphnodes, 627–629

tumor-infiltrating lymphocytes,624–627

solid. See Solid tumors.

U

Universal bystander cells, gene transfer-based immunotherapeutic approachesto pancreatic cancer using, 542–543

Urologic cancers, approved cancer genetherapy trials in, 804–822

V

Vaccines, in cancer gene therapy, cytokine-modified tumor, 681–696

future directions, 692–693identifying tumor-specific

antigens, 685–687incorporating into other

treatment modalities,691–692

results with, in clinical trials,687–691

role for immune system in tumorrejection, 682–685

dendritic cell, 648–649genetically modified tumor, 503–505

Vaccinia virus, as a vector for cancer genetherapy, 509–510oncolytic, basic viral biology of, 664

clinical studies with, 675

Vector systems, for cancer gene therapy,505–512, 621–623

adeno-associated virus, 510–511adenovirus, 507–508

herpes simplex virus, 508–509molecular conjugates versus,

710–712nonviral gene delivery systems,

511–512, 622–623retrovirus, 505–507vaccinia virus, 509–510

for head and neck cancer gene therapy,590–592nonviral, 591–592viral, 590–591

Viral oncolysis. See Viruses, oncolytic.

Viral replication, selective, in gene therapyof pancreatic cancer, 552–553

Viral vectors. See Vector systems.

Virus-directed enzyme prodrug therapy,501–502

Viruses, endosomal lysis agents in protein/DNA polyplexes, for cancer genetherapy, 705–707oncolytic, in cancer gene therapy,

502–503, 661–680basic viral biology, 663–664

adenovirus, 663herpes simplex virus, 663Newcastle disease virus, 664reovirus, 664vaccinia virus, 664

clinical studies, 671–676adenovirus, 673–674herpes simplex virus,

674–675Newcastle disease virus,

675–676vaccinia virus, 675

historical background, 661–663preclinical studies, 664–671

optimizing antitumorefficacy, 668–671

optimizing tumor-specificreplication, 664–668

replication-selective, future directionsin use of, 584–585

834 Index / Surg Oncol Clin N Am 11 (2002) 827–834