Mutation-Selective Tumor Remission with Ras-Targeted, Whole Yeast-Based Immunotherapy

Abstract

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 carcinogeninduced 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.

Saccharomyces as a vaccine against systemic aspergillosis: ‘the friend of man’ a friend again?

“…We should note, however, that heat-killed Saccharomyces has been studied in man as a vehicle for delivering tumour antigens, and subcutaneous administration did not exhibit dose-limiting toxicity in phase I human clinical trials (Franzusoff et al, 2005;Lu et al, 2004;Munson et al, 2007), raising the possibility of efficacy of HKY itself as a panfungal vaccine in man.…”

Advanced Pancreatic Cancer: Flourishing Novel Approaches in the Era of Biological Therapy

“…GI-4000 is whole, heat-killed recombinant Saccharomyces cerevisiae yeast that expresses mutated RAS proteins [92]. After administration, the yeast-expressed mutated Ras protein is digested intopeptidesfor bothmajorhistocompatibilitycomplex class Iand II pathways ofantigenpresentation toproduce ahighly specific and potent T-cell response.…”

“…The CD8 killer T cells are activated to provide systemic surveillance and to selectively eliminate tumor cells that express the mutated Ras. In preclinical testing using mice bearing Ras-mutated tumor, this immunotherapy demonstrated dose-dependent elimination of tumors [92]. This drug has been tested in phase I trial with a satisfactory safety profile [93].…”

Delivery of functional DNA and messenger RNA to mammalian phagocytic cells by recombinant yeast

“…9,10 Yeast has been repeatedly shown to generate adaptive (including cell-mediated) immune responses in mice [11][12][13][14][15][16][17][18][19] and also in humans. 20 In contrast to the majority of attenuated bacteria and mammalian viruses (which are already under investigation as DNA/RNA carriers, for example, Listeria), several yeast genera possess the GRAS ('generally regarded as safe') status, which would facilitate the approval of a yeast-based vaccine considerably.…”