History

CONTINENT

PROTOCOLS

PATIENTS

NUMBER

%

NUMBER

%

America

310

72.9

2383

68.6

Europe

97

22.8

727

20.9

Asia

9

2.1

37

1.1

Australia

3

0.7

13

0.4

Africa

1

0.2

15

0.4

Multi-continent

5

1.2

301

8.7

Total

425

100

3476

100

COUNTRY

PROTOCOLS

PATIENTS

NUMBER

%

NUMBER

%

Australia

2

0.4

11

0.3

Austria

2

0.4

15

0.4

Canada

11

2.6

120

3.5

China

2

0.4

4

0.1

Egypt

1

0.2

15

0.4

Finland

3

0.7

33

0.9

France

15

3.5

102

2.9

Germany

9

2.1

87

2.5

Israel

1

0.2

0

0

Italy

7

1.6

45

1.3

Japan

3

0.7

5

0.1

Korea

1

0.2

9

0.3

Netherlands

5

1.2

82

2.4

New Zealand

1

0.2

2

<0.1

Poland

1

0.2

30

0.9

Singapore

2

0.4

19

0.6

Spain

2

0.4

33

0.9

Sweden

2

0.4

6

0.2

Switzerland

7

1.6

34

1

United Kingdom

44

10.4

260

7.5

USA

299

70.4

2263

65.1

Multi-country

5

1.2

301

8.7

Total

425

100

3476

100

　

CATEGORY

PROTOCOLS

PATIENTS

NUMBER

%

NUMBER

%

Monogenic diseases

55

12.9

306

8.8

Cancer

279

65.6

2459

70.7

Infectious diseases

33

7.8

412

11.9

Other diseases

16

3.8

66

1.9

Gene marking

40

9.4

227

6.5

Healthy volunteers

2

0.5

6

0.2

Total

425

100

3476

100

　

CATEGORY

SPECIFIC CONDITION

Monogenic diseases

AAT deficiency

ADA-SCID

Canavan disease

Chronic granulomatous disease

Cystic fibrosis

Familial hypercholesterolemia

Fanconi's anemia

Gaucher's disease

Hemophilia B

Hunter's syndrome (mucopolysaccharidosis type II)

Hurler syndrome (mucopolysaccharidosis type I)

Leukocyte Adherence Deficiency

OTC deficiency

Purine nucleoside phosphorylase deficiency

X-linked SCID

Cancer

Gynecological tumors (breast, ovary, cervix)

Nervous system tumors (glioblastoma, leptomeningeal carcinomatosis, glioma, astrocytoma, neuroblastoma)

Gastrointestinal tumors (colon, colorectal, liver metastases, post-hepatitis liver cancer, pancreatic cancer)

Genito-urinary tumors (prostate, renal carcinoma)

Skin tumors (melanoma)

Head and neck tumors

Lung tumors (adenocarcinoma, small cell cancer, non-small cell cancer)

Mesothelioma

Hematological malignancies (leukemias, lymphomas, GVHD risk after alllogeneic BMT in leukemia, multiple myeloma)

Sarcomas

Germ cell cancers

Infectious diseases

HIV infection

Other diseases

Amyotrophic lateral sclerosis

Coronary artery disease

Cubital tunnel syndrome

Peripheral artery disease

Restenosis (accelerated endothelialization and reduced neointimal thickening)

Rheumatoid arthritis

Gene marking

GvHD control after allogeneic BMT

Acute hepatic failure

Hematological malignancies
(acute myelogenous leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, follicular non-Hodgkin's lymphoma, EBV+ Hodgkin's disease, multiple myeloma)

Various advanced cancers

Breast cancer, Ovarian cancer

HIV infection

Melanoma

Renal carcinoma, bladder cancer

Neuroblastoma

Non-small cell lung cancer

Pediatric malignancies

Healthy volunteers

Immune response to gene delivery system

VECTOR

PROTOCOLS

PATIENTS

NUMBER

%

NUMBER

%

Adeno-Associated Virus

4

0.9

36

1

Adenovirus

86

20.2

534

15.4

Electroporation

2

0.5

20

0.6

Gene gun

4

0.9

35

1

Herpesvirus

1

0.2

0

0

Lipofection

75

17.6

757

21.8

Lipofection / AAV

2

0.5

0

0

Lipofection / Adenovirus

1

0.2

3

<0.1

Naked DNA

16

3.8

71

2

Poxvirus

25

5.9

130

3.7

Retroviral vector producing cells

20

4.7

408

11.7

Retrovirus

160

37.6

1222

35.2

Retrovirus / Gene gun

1

0.2

6

0.2

RNA transfer

1

0.2

30

0.9

Vaccinia virus

5

1.2

40

1.2

Other transfections

7

1.7

101

2.9

N/C

15

3.5

83

2.4

Total

425

100

3476

100

GENE TYPE

PROTOCOLS

PATIENTS

NUMBER

%

NUMBER

%

Cytokine

67

15.8

614

17.7

Antigen

64

15.1

894

25.7

Suicide

51

12

567

16.3

Deficiency

51

12

289

8.3

Marker

39

9.2

215

6.2

Tumor suppressor

24

5.6

199

5.7

Receptor

17

4

107

3.1

Others

37

8.7

129

3.7

Multiple genes

51

12

304

8.7

N/C

24

5.6

158

4.5

Total

425

100

3476

100

GENE TYPE

GENE

Antibody

sFv against erbB2

sFv against rev

sFv anti-env

Specific anti-idiotype

TcR Ab

Antigen

CEA

env / rev

gp100

HIV-IT(V) env / rev

HLA-B7

HLA-B7 / b2m

MART-1

MUC-1

PSA

HLA-A2 or HLA-B13 or H-2K(k)

Antigen + marker

CEA / KanaR

HLA-B7 / NeoR

Antisense

Antisense to c-fos or c-myc

Antisense to IGF-1

Antisense to TAR

Antisense to Pol 1

Antisense to tat and rev

Antisense to TGF-b2

Antisense + drug resistance

Antisense to BCR/ABL + DHFR

Antisense or decoy + negative transdominant

Antisense to TAR / revTD

RSV-TAR / revM10

Antisense + tumor suppressor

p53 / k-ras antisense

Antitumoral

E1A

Cytokine

GM-CSF

IFNa

IFNb

IFNg

IFNg / IL-2

IL-12

IL-2

IL-2 / GM-CSF

IL-2 / HLA-B7

IL-2 / lymphotactin

IL-4

IL-6 / sIL-6R

IL-7 / IL-12 / GM-CSF

IL-7 / IL-2

Cytokine + marker

IL-12 / NeoR

IL-2 / NeoR

LacZ / IL-2

TNF / NeoR

Decoy

RRE / polyTAR

Decoy + marker

NeoR or RRE decoy

RRE / polyTAR / NeoR

Deficiency

AAT

ADA

ASPA

CD18

CD154

CFTR

Common gamma chain

FACC

factor IX

GC

gp91phox

IDS

IDUA

LDLR

OTC

p47phox

PNP

Deficiency + marker

ADA / NeoR

Drug resistance

MDR-1

MGMT

Drug resistance + marker

MDR-1 / NeoR

Marker

Hy

LacZ

NeoR

Multiple

IL-7 / TK / Hy

TK-NeoR + deltaLNGFR

Negative transdominant

Trev

Oncogene regulator

HER-2/neu

Others

CNTF

FGF-4

hIGF-1

IRAP

VEGF

Other + marker

LacZ / VEGF

Receptor

CC49-Zeta TcR

CD4-Zeta chimera

CD80 (B7-1)

Mov-gamma

Ribozyme

Anti HIV-tat and Rev

Anti HIV-Tat ribozyme

Anti HIV-ribozyme

Suicide

CD

Staphylococcus Enterotoxin B

TK

Suicide + marker

Hy / TK

LacZ / TK

TK / NeoR

Tumor suppressor

BRCA1

p53

Rb

SOURCE OF TARGET CELLS

PROTOCOLS

PATIENTS

NUMBER

%

NUMBER

%

Autologous

350

82.4

2932

84.3

Allogeneic

29

6.8

244

7

Syngeneic

5

1.2

61

1.8

Autologous/Allogeneic

3

0.7

14

0.4

Allogeneic/Syngeneic

1

0.2

8

0.2

Xenogeneic

3

0.7

30

0.9

N/C

34

8

187

5.4

Total

425

100

3476

100

ROUTE

PROTOCOLS

PATIENTS

NUMBER

%

NUMBER

%

Bone marrow transplantation

43

10.1

244

7

Intraarterial

5

1.2

47

1.4

Intraarticular

2

0.5

7

0.2

Intrabronchial

7

1.6

66

1.9

Intracoronary

4

0.9

0

0

Intracranial

2

0.5

0

0

Intradermal only

16

3.8

85

2.4

Intradermal and intramuscular

3

0.7

21

0.6

Intradermal and subcutaneous

4

0.9

30

0.9

Intrahepatic

4

0.9

20

0.6

Intramuscular only

19

4.5

343

9.9

Intranasal

20

4.7

167

4.8

Intraperitoneal only

15

3.5

117

3.4

Intraperitoneal and Intrapleural

2

0.5

18

0.6

Intrapleural only

2

0.5

31

0.9

Intraprostatic

1

0.2

0

0

Intrathecal

1

0.2

12

0.3

Intratumoral

115

27.1

1282

36.9

Intravenous only excluding BMT

70

16.5

309

8.9

Intravenous and intraperitoneal

1

0.2

2

<0.1

Intraventricular (CNS)

2

0.5

3

<0.1

Intravesical

2

0.5

5

0.1

Subcutaneous only

51

12

509

14.6

Subcutaneous and intramuscular

1

0.2

7

0.2

N/C

33

7.8

151

4.3

Total

425

100

3476

100

	HUMAN GENE MARKER/THERAPY CLINICAL PROTOCOLS (U.S. and Other Countries 2001!)

Earlier Data:
	Countries where trials are being performed
	Diseases addressed
	Vectors used
	Genes transferred
	Cell types
	Routes of administration
	Phases of clinical trials