Fusion of a tumour-associated antigen to HIV-1 Tat improves protein-based immunotherapy of cancer.
BACKGROUND
The ultimate success of cancer vaccination is primarily dependent upon the generation of tumour-specific CTLs. Protein-based vaccination, while safe, poorly elicits such CTL responses. As fusion of an antigen to the HIV-1 Tat transduction domain was reported to increase MHC class I presentation and CTL responses in vitro, we tested the potency of this approach to augment tumour-directed responses.


METHODS
Human papillomavirus type 16 (HPV16) E7 proteins, fused (E7-Tat) or not (E7) to Tat carboxy-terminal region, were produced and studied in vitro and in vivo.


RESULTS
E7-Tat, not E7, penetrated the cell membrane and was transcriptionally active. In vitro, E7-Tat induced higher IFN-gamma production from E7-specific T-cells than E7. In C57BL/6 mice, E7-Tat mixed with Quil A generated enhanced prophylactic and therapeutic suppression of HPV16-positive C3 tumour outgrowth. Similar, but greatly enhanced E7-specific effector and helper T-cell responses were elicited following E7-Tat/Quil A rather than E7/Quil A vaccination.


CONCLUSIONS
This study offers a new strategy for improving subunit cancer vaccines.
Giannouli
Christina
C
Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium.
Brulet
Jean-Marc
JM
Gesché
Fabienne
F
Rappaport
Jay
J
Burny
Arsène
A
Leo
Oberdan
O
Hallez
Sophie
S
D016475:3T3 Cells; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D062605:Quillaja Saponins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D012503:Saponins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D015696:Gene Products, tat; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D062605:Quillaja Saponins; D011993:Recombinant Fusion Proteins; D012503:Saponins; C059731:oncogene protein E7, Human papillomavirus type 16; C046386:Quil A; D007371:Interferon-gamma