CoChat
Sign Up
Cited by 41Immunotherapy and Immune ResponsesBacterial Cancer TherapyCancer Immunotherapy and Biomarkers

The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.

Whole Recombinant Saccharomyces cerevisiae Yeast Expressing Ras Mutations as Treatment for Patients With Solid Tumors Bearing Ras Mutations: Results From a Phase 1 Trial

Open access
Cohn, Allen, Morse, Michael A., O’Neil, Bert, Whiting, Samuel, Coeshott, Claire, Ferraro, John, Bellgrau, Donald, Apelian, David, Rodell, Timothy C.·2018·Journal of Immunotherapy
DOI 10.1097/cji.0000000000000219PMC PMC5895167
Open this paper in CoChat — free account

Abstract

We are developing whole, heat-killed, recombinant Saccharomyces cerevisiae yeast, engineered to encode target proteins, which stimulate immune responses against malignant cells expressing those targets. This phase 1 trial, enrolling patients with advanced colorectal or pancreas cancer, was designed to evaluate safety, immunogenicity, response, and overall survival of ascending doses of the GI-4000 series of products, which express 3 different forms of mutated Ras proteins. The study enrolled 33 heavily pretreated subjects (14 with pancreas and 19 with colorectal cancer), whose tumors were genotyped before enrollment to identify the specific ras mutation and thereby to identify which GI-4000 product to administer. No dose limiting toxicities were observed and no subject discontinued treatment due to a GI-4000 related adverse event (AE). The majority of AEs and all fatal events were due to underlying disease progression and AE frequencies were not significantly different among dose groups. GI-4000 was immunogenic, as Ras mutation-specific immune responses were detected on treatment in ∼60% of subjects. No objective tumor responses were observed but based on imaging, clinical status and/or biochemical markers, stable disease was observed in 6 subjects (18%) on day 29, while 1 subject had stable disease at days 57 and 85 follow-up visits. The median overall survival was 3.3 months (95% confidence interval, 2.3–5.3 mo), and 5 subjects survived past the 48-week follow-up period. No significant dose-dependent trends for survival were observed. This first clinical trial in humans with GI-4000 demonstrated a favorable safety profile and immunogenicity in the majority of subjects.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1097/cji.0000000000000219

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Figures

FIGURE 1 Subject disposition. FU indicates follow-up; YU, yeast units.
FIGURE 1 Subject disposition. FU indicates follow-up; YU, yeast units.CC BY-NC-ND · PubMed Central
FIGURE 2 Representative lymphocyte proliferation assay (LPA) responses. LPA responses are shown as stimulation indices for 3H-thymidine uptake in peripheral blood mononuclear cells following stimulation with Ras peptide pools at baseline (day 1) and at up to 6 timepoints following initiation of treatment with GI-4000. Dotted line indicates a stimulation index of 2, the cut off for responsiveness. Fourteen of 19 subjects with proliferative responses ≥2 are shown. The additional 5 subjects deemed responders by LPA are not shown either because only 1 on treatment sample day was available (n=3) or because the baseline response was not exceeded by the on treatment responses (n=2). Top row: responses of 5 long-term survivors who survived beyond the 48 week follow-up period. YU indicates yeast unit.
FIGURE 2 Representative lymphocyte proliferation assay (LPA) responses. LPA responses are shown as stimulation indices for 3H-thymidine uptake in peripheral blood mononuclear cells following stimulation with Ras peptide pools at baseline (day 1) and at up to 6 timepoints following initiation of treatment with GI-4000. Dotted line indicates a stimulation index of 2, the cut off for responsiveness. Fourteen of 19 subjects with proliferative responses ≥2 are shown. The additional 5 subjects deemed responders by LPA are not shown either because only 1 on treatment sample day was available (n=3) or because the baseline response was not exceeded by the on treatment responses (n=2). Top row: responses of 5 long-term survivors who survived beyond the 48 week follow-up period. YU indicates yeast unit.CC BY-NC-ND · PubMed Central
FIGURE 3 mRNA expression in peripheral blood mononuclear cells restimulated with Ras peptide pools. One subject in the 20 YU group (with G12V ras mutation) survived beyond the 48 week follow-up period. Bars show relative increases in expression of GM-CSF, IFN-γ, and TNF-α mRNA compared with unstimulated controls following stimulation of peripheral blood mononuclear cells with Ras G12V peptide pools (A) or CEF peptides (B) at 2 µg/mL final concentration. GM-CSF indicates granulocyte-macrophage colony stimulating factor.
FIGURE 3 mRNA expression in peripheral blood mononuclear cells restimulated with Ras peptide pools. One subject in the 20 YU group (with G12V ras mutation) survived beyond the 48 week follow-up period. Bars show relative increases in expression of GM-CSF, IFN-γ, and TNF-α mRNA compared with unstimulated controls following stimulation of peripheral blood mononuclear cells with Ras G12V peptide pools (A) or CEF peptides (B) at 2 µg/mL final concentration. GM-CSF indicates granulocyte-macrophage colony stimulating factor.CC BY-NC-ND · PubMed Central
FIGURE 4 Overall survival based on Kaplan-Meier analyses of all enrolled subjects.
FIGURE 4 Overall survival based on Kaplan-Meier analyses of all enrolled subjects.CC BY-NC-ND · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 29 references

Cited by

Sorted by citations

See all 41

Related

Metadata

Authors
Cohn, A., Morse, M. A., O’Neil, B., Whiting, S., Coeshott, C., Ferraro, J., Bellgrau, D., Apelian, D., & Rodell, T. C.
Affiliations
  • Rocky Mountain Cancer Centers (US)
  • Duke Medical Center (US)
  • Indiana University Melvin and Bren Simon Comprehensive Cancer Center (US)
  • Fred Hutch Cancer Center (US)
  • GlobeImmune (United States) (US)
  • University of Colorado Denver (US)
Corresponding author
Cohn, Allen
ORCID
Venue
Journal of Immunotherapy
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2018-04
Volume
41
Issue
3
Pages
141-150
ISSN
1524-9557 (ISSN-L)
DOI
10.1097/cji.0000000000000219
PMC
PMC5895167
OpenAlex
W2792687062
Cited by
41
References
29
Citations by year
2026: 6 · 2025: 9 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 5
FWCI
1.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Immunotherapy (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
recombinant Saccharomyces cerevisiae, RAS mutations, colorectal cancer, pancreatic cancer, solid tumors, tumor-specific immunity, vaccine safety, immunogenicity, overall survival, stable disease
MeSH terms
Adult, Aged, Biological Therapy, Complement Activation, Female, Humans, Immunity, Male, Middle Aged, Mutation, Neoplasms, Saccharomyces cerevisiae, Biomarkers, Tumor, Gene Expression, Gene Expression Regulation, Neoplastic, ras Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review