Mutation-selective tumor remission with Ras-targeted, whole yeast-based immunotherapy.
Activating mutations in Ras oncoproteins represent attractive targets for cancer immunotherapy, but few vectors capable of generating immune responses required for tumor killing without vector neutralization have been described. Whole recombinant yeast heterologously expressing mammalian mutant Ras proteins were used to immunize mice in a carcinogen-induced lung tumor model. Therapeutic immunization with the whole recombinant yeast caused complete regression of established Ras mutation-bearing lung tumors in a dose-dependent, antigen-specific manner. In combination with the genomic sequencing of tumors in patients, the yeast-based immunotherapeutic approach could be applied to treat Ras mutation-bearing human cancers.
Lu
Yingnian
Y
GlobeImmune Inc., 12635 E. Montview Boulevard, Aurora, CO 80010, USA.
Bellgrau
Donald
D
Dwyer-Nield
Lori D
LD
Malkinson
Alvin M
AM
Duke
Richard C
RC
Rodell
Timothy C
TC
Franzusoff
Alex
A
D000236:Adenoma / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000276:immunology* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000502:physiology; D014520:Urethane
D004273:DNA, Neoplasm; D011994:Recombinant Proteins; D014520:Urethane; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)