Immunization with DNA coding for gp100 results in CD4 T-cell independent antitumor immunity.
BACKGROUND
Xenogeneic DNA immunization can exploit small differences in expressed protein sequence resulting in immune recognition of self-molecules. We hypothesized that immunizing mice with xenogeneic DNA coding for the human melanosomal membrane glycoprotein gp100 would overcome immune ignorance or tolerance and result in tumor immunity. We also investigated the immunologic mechanisms of the antitumor immunity.


METHODS
C57BL/6 mice were immunized with DNA coding for human gp100, mouse gp100, or control vector by gene gun. After immunization, mice were challenged with a syngeneic melanoma expressing gp100, and tumor growth was analyzed. Mice deficient in major histocompatibility complex class I or class II molecules were similarly studied to assess the immunologic mechanism of the tumor protection.


RESULTS
There was significant tumor protection after vaccination with xenogeneic human gp100 DNA. Class I, but not class II, major histocompatibility complex molecules were required for tumor immunity. In addition, mice immunized with human gp100 demonstrated autoimmunity manifested as coat color depigmentation.


CONCLUSIONS
Immunization with xenogeneic DNA coding for the melanosomal glycoprotein gp100 results in tumor protection and autoimmune depigmentation. These results show that xenogeneic DNA vaccines can lead to cancer immunity without CD4(+) T-cell help with potential implications for rational vaccine design.
Swim Across America Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
W G
WG
Hawkins
J S
JS
Gold
R
R
Dyall
J D
JD
Wolchok
A
A
Hoos
W B
WB
Bowne
R
R
Srinivasan
A N
AN
Houghton
J J
JJ
Lewis
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000556:secondary*; D008285:Major Histocompatibility Complex; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D011994:Recombinant Proteins; D016415:Sequence Alignment; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA; D058951:gp100 Melanoma Antigen
D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; C548642:Pmel protein, mouse; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D058951:gp100 Melanoma Antigen; D016178:Granulocyte-Macrophage Colony-Stimulating Factor