Table 1.
Different Strategies Utilized With Tumor Endothelial Vaccines
| 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] |
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