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Table 1 Different Strategies Utilized With Tumor Endothelial Vaccines

From: Vaccines targeting the neovasculature of tumors

TARGET

FORM OF THE VACCINE

TUMORS

Vector/Route

MECHANISMS

Other Comments

REFERENCES

Endothelial Cell Targets

VEGFR2

mVEGFR2-AP fusion protein

Melanoma and lung carcinoma

DC pulsed

Ab, CTL

Primarily CD8+

P

Li Y et al., 2002

[45]

 

Autologous DNA vaccine- full-length mVEGFR2

Melanoma, colon carcinoma, non-small cell lung carcinoma, hepatoma

S. typhimurium, oral

CTL

Modest delay in wound healing

P, T

Niethammer AG et al., 2002 [59]

 

Xenogeneic DNA vaccine

Murine melanoma, carcinoma, fibrosarcoma, lyphoma

"Naked" DNA,

SC

Ab, CTL, CD4+(Th1)-mediated

Quail VEGFR2 vaccine

Increased levels of IgG2a and 2b

P, T

Liu, J-Y et al., 2003

[130]

 

Autologous DNA vaccine- mVEGFR2 fragment

Breast tumor-rat Her2 expressing carcinoma; murine p53- deficient breast carcinoma

L. monocytogenes, oral

CD8+ mediated Inf-γ Elispot

Encodes listerolysin-VEGFR2 fragment; No effect on wound healing or pregnancy

P, T

Seavey MM et al., 2009 [32]

 

Autologous DNA minigene

Murine breast and colon carcinomas

S. typhimurium, oral

CTL

Encodes H-2Kd or H-2Dd restricted peptides

P

Luo Y et al., 2007 [63]

 

Autologous DNA minigene

Murine lung, prostate, and breast cancers

S. typhimurium, oral

CTL

Plasmid also encodes HIV-TAT peptide

P

Zhou H et al., 2005 [61]

 

H-2Db -restricted Peptides

Murine colon carcinomas

SC

CTL

adjuvant (GM-CSF, CD40 Ab);

T

Dong Y et al., 2006

[62]

 

HLA-A2 or-A24 restricted hVEGFR2 Peptides

Mouse melanoma and colon carcinomas

ID

CTL

HLA-24 restricted Peptide 169 (RFVPDGNRI) induced human PBMC-CTL lysis of endothelial cells

Wada S et al., 2005 [43]

 

VEGFR2 Peptide 169 + gemcitabine

Pancreatic cancer

(Phase I)

SC

CTL;

Reduced Treg cells

Adjuvant (IFA)

Miyazawa M. et al., 2009 [66]

 

Xenogeneic DNA vaccine

Murine breast and colon carcinoma

Cationic liposomes, IV

Ab, CTL

Human VEGFR2;

P, T

Xie K et al., 2009 [65]

 

Autologous DNA vaccine (VEGFR2 fused with β-defensin 2)

Murine lung and colon cancer

Cationic liposomes, IM

Ab, CTL

Antitumor and anti-angiogenic synergy between VEGFR2 and β-defensin-2;

P, T

Wang YS et al., 2007 [64]

 

Autologous DNA vaccine- Extracellular Domain

Murine Lung

S. typhimurium, oral

Ab, CTL CD4+ (Th1), C8+ mediated

Increased levels of IgG2a and 2b

P

Zuo SG et al., 2010 [67]

VEGF

Xenogeneic DNA

vaccine

Fibrosarcoma, breast cancer, hepatoma

"Naked" DNA,

IM

Ab

CD4+-mediated

Xenopus VEGF has about 75% homology with humans and mice

P, T

Wei YQ et al., 2001 [58]

 

Autologous or xenogeneic protein

Murine and human colon caricinoma; human rhadosarcoma

IM

Ab;

h- or mVEGF conjugated to KLH

P

Rad FH et al., 2007 [73]

FGFR-1/bFGF

Autologous bFGF peptide

Murine melanoma and lung carcinoma

Lipid A containing liposomes

IM

Ab

Effective vaccine against the 44 aa segment of the heparin binding domain; No effect on wound healing or pregancy

P

Plum SM et al., 2000 [76]

Plum SM et al., 2004 [77]

 

Xenogeneic DNA

vaccine

Murine fibrosarcoma, hepatoma and breast cancer

"Naked" DNA, IM

Ab

FGFR-1 from Xenopus laevis

Delayed wound healing

P, T

He QM et al., 2003 [78]

TEM8

Autologous TEM8 with rat Her2 or human tyrosinase-related protein1 DNA vaccine

Rat Her-2 expressing breast carcinoma;

Murine melanoma

Gold-particle gene gun

No Ab or CTL response with TEM8 vaccine alone

Synergy observed

P

Felicetti P et al., 2007 [82]

 

Xenogeneic DNA vaccine

Murine melanoma

S. typhimurium

oral

CTL;

Human TEM8

No effect on wound healing

T

Ruan Z et al., 2009 [83]

ENDOGLIN (CD105)

Xenogeneic protein

Murine lung, melanoma, colon carcinoma, fibrosarcoma

SC

Ab;

Synergy with cis-platinum; adjuvant (alum)

P, T

Tan GH et al., 2004 [87]

Tan GH et al., 2004 [88]

ANGIOMOTIN

Xenogeneic DNA vaccine, full-length

Her-2 expressing breast cancer in transgenic mice

Electroporation,

TC

Ab

Human angio-motin and Her-2; antitumor synergy when combined with Her-2 DNA vaccine

Holmgren L et al., 2006 [38]

TIE2

Xenogeneic protein vaccine

Murine hepatomas and melanomas

SC

Ab

Chicken Tie2

P, T

Luo Y et al., 2006 [94]

 

DNA vaccine encoding HLA-restricted peptides

In vitro lysis of endothelial cells expressing Tie-2; Tumor response not tested

Gold-particle gene gun

CTL

HLA-A*0201/Kb transgenic mice; the epitope

(FLPATLTMV) had the highest CTL response;

Ramage JM et al., 2004 [95]

HP59/SP55

Xenogeneic peptides

Murine lung carcinoma

Not stated

Ab

HP59 and SP55 peptide mixture

P

Fu C et al., 2001 [96]

Pericyte Targets

HMW-MAA

Xenogeneic DNA vaccine, HMW-MAA fragment

Murine melanoma, renal carcinoma, Her-2 transgenic mice

L monocytogenes

IP

Ab, CTL

HMW-MAA (2160-2225 aa) fragment fused to LLO

T

Maciag PC et al., 2008 [33]

PDGFRβ

Autologous DNA vaccine, full-length

Murine colon, breast, lung carcinoma

S. typhimurium

oral

CTL

Also, targets activated fibroblasts

P, T

Kaplan CD et al., 2006 [34]

Combined Targets

SURVIVIN

Xenogeneic DNA vaccine

Murine melanoma

Electroporation, ID

CTL

Human survivin vaccine

P

Lladser A et al., 2010 [37]

 

Survivin/CCL21 DNA vaccine

Murine lung carcinoma

S. typhimurium, oral

CTL

Mouse survivin; no effect on wound closure or fertility

P, T

Xiang R et al., 2005 [35]

GRP

Recombinant chimeric HSP-65 -GRP6 fusion protein

Murine breast carcinomas

SC

Ab, CTL

6 tandem repeats of GRP(18-27 aa) fused to HSP-65

P, T

Guojun W et al., 2008 [115]

 

Chimeric-HSP65-GRP6 DNA Vaccine

Murine melanoma

"Naked" DNA, IM

Ab

chimera also includes tetanus toxoid and HSP70 fragments;

P

Fang J et al., 2009 [116]

LEGUMAIN

Allogeneic DNA vaccine

Murine non-small lung, colon and breast cancers

S. typhimurium, oral

CTL

Mutant polyubiquitin incorporated

P, T

Luo Y et al., 2006

[119]

 

Autologous DNA minigene

Murine breast carcinoma

S. typhimurium, oral

CTL

Angiogenesis inhibited more 90%; H-2K vaccine more potent than H-2D

P

Lewen S et al., 2008 [120]

MMP-2

Xenogeneic full-length MMP-2 DNA vaccine

Murine fibrosarcoma, hepatoma, lung carcinoma

"Naked" DNA, IM

Ab

Chicken MMP-2

P, T

Su JM et al., 2003 [123]

β3 Integrin

Xenogeneic β3 DNA vaccine

Murine fibrosarcoma, mammary carcinoma

"Naked" DNA, IM

Ab

Chicken β3 ligand binding domain

P, T

Lou YY et al., 2002 [129]

  1. Abbreviations in table; Ab, antibody response; AP-alkaline phosphatase; CTL, cytotoxic T-lymphocyte response; m, mouse; h, Human; LLO, listerolysin; P, protective vaccine approach in which pre-immunized mice show anti-tumor activity; T, therapeutic vaccine approach in which vaccine, administered after tumor inoculation, has anti-tumor efficacy; keyhole limpet hemocyanin; SC, subcutaneous, ID, intradermal, IM, intramuscular, TC, transcutaneous