Treatment of Ras mutation-bearing solid tumors using whole recombinant S. cerevisiae yeast expressing mutated Ras: Preliminary safety and immunogenicity results from a phase 1 trial

2571 Background: A number of tumors express activating, transforming mutations at codons 12 and 61 in the ras oncogene. We have previously shown that whole heat-inactivated recombinant S. cerevisiae expressing mutated Ras proteins induce protective cellular immunity as well as complete remission of established, carcinogen-induced, ras mutation-bearing lung tumors in mice (Cancer Res 64, 5084, 2004). Methods: GI-4014, GI-4015 and GI-4016 are recombinant yeast, each expressing a truncated and modified human Ras protein containing one of the three most common mutations at codon 12 (G12V, G12C, or G12D respectively) and the two most common mutations at codon 61 (Q61R and Q61L). In a four center Phase 1 trial, patients with advanced colorectal, pancreatic or non-small cell lung cancer, who have failed at least first line chemotherapy, have tumor samples subjected to genomic sequencing of the K-, H- and N-ras genes. If the tumor contains one of the target mutations, the subject receives 5 subcutaneous weekly do...