The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
p53MVA Therapy in Patients with Refractory Gastrointestinal Malignancies Elevates p53-Specific CD8+ T-cell Responses
Open accessPublished version of a preprint
Abstract
Purpose: To conduct a phase I trial of a modified vaccinia Ankara (MVA) vaccine delivering wild-type human p53 (p53MVA) in patients with refractory gastrointestinal cancers. Experimental Design: Three patients were vaccinated with 1.0 × 108 plaque-forming unit (pfu) p53MVA followed by nine patients at 5.6 × 108 pfu. Toxicity was classified using the NCI Common Toxicity Criteria and clinical responses were assessed by CT scan. Peripheral blood samples were collected pre- and post-immunization for immunophenotyping, monitoring of p53MVA-induced immune response, and examination of PD1 checkpoint inhibition in vitro. Results: p53MVA immunization was well tolerated at both doses, with no adverse events above grade 2. CD4+ and CD8+ T cells showing enhanced recognition of a p53 overlapping peptide library were detectable after the first immunization, particularly in the CD8+ T-cell compartment (P = 0.03). However, in most patients, this did not expand further with the second and third immunization. The frequency of PD1+ T cells detectable in patients' peripheral blood mononuclear cells (PBMC) was significantly higher than in healthy controls. Furthermore, the frequency of PD1+ CD8+ T cells showed an inverse correlation with the peak CD8+ p53 response (P = 0.02) and antibody blockade of PD1 in vitro increased the p53 immune responses detected after the second or third immunizations. Induction of strong T-cell and antibody responses to the MVA backbone were also apparent. Conclusion: p53MVA was well tolerated and induced robust CD8+ T-cell responses. Combination of p53MVA with immune checkpoint inhibition could help sustain immune responses and lead to enhanced clinical benefit. Clin Cancer Res; 20(17); 4459–70. ©2014 AACR.
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.
Integrity signals
Registry
Cites
Statistics
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.
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?
In the citing paper
“Later in 2014 and 2018, Hardwick’s group conducted two early-phase clinical trials involving a modified vaccinia virus ankara vaccine encoding wtp53 (MVAp53 (253)). The studies showed that MVAp53 could induce CD8+ and CD4+ T cell responses in patients with refractory gastrointestinal cancer and ovarian cancer, respectively.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [593]
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
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
Nivolumab plus Ipilimumab in Advanced Melanoma
Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., Segal, N. H., Ariyan, C. E., Gordon, R.-A., Reed, K., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302369 · Cited by 4,230
Iwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., & Minato, N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192461099 · Cited by 3,261
Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity
Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.12.009 · Cited by 1,347
The Central Role of CD4+ T Cells in the Antitumor Immune Response
Hung, K., Hayashi, R., Lafond-Walker, A., Lowenstein, C., Pardoll, D., & Levitsky, H. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.12.2357 · Cited by 1,345
Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity
Hirano, F., Kaneko, K., Tamura, H., Dong, H., Wang, S., Ichikawa, M., Rietz, C., Flies, D. B., Lau, J. S., Zhu, G., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.1089.65.3 · Cited by 1,018
p53 and Human Cancer: The First Ten Thousand Mutations
Hainaut, P. L., & Hollstein, M. C. (1999) · Advances in cancer research · doi:10.1016/s0065-230x(08)60785-x · Cited by 999
PROVENGE (Sipuleucel-T) in Prostate Cancer: The First FDA-Approved Therapeutic Cancer Vaccine
Cheever, M. A., & Higano, C. S. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3126 · Cited by 780
The anticancer immune response: indispensable for therapeutic success?
Zitvogel, L., Apétoh, L., Ghiringhelli, F., André, F., Tesnière, A., & Kroemer, G. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35180 · Cited by 588
Gabitass, R. F., Annels, N. E., Stocken, D. D., Pandha, H., & Middleton, G. (2011) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-011-1028-0 · Cited by 574
Cited by
Sorted by citations
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396
Hardwick, N. R., Frankel, P., Ruel, C., Kilpatrick, J., Tsai, W., Kos, F., Kaltcheva, T., Leong, L., Morgan, R., Chung, V., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2709 · Cited by 66
Self-citationYuan, Y., Kos, F. J., He, T.-F., Yin, H. H., Li, M., Hardwick, N., Zurcher, K., Schmolze, D., Lee, P., Pillai, R. K., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1363138 · Cited by 23
Self-citationOvercoming immunosuppression to enhance a p53MVA vaccine
Hardwick, N., Chung, V., Cristea, M., Ellenhorn, J. D., & Diamond, D. J. (2014) · OncoImmunology · doi:10.4161/21624011.2014.958949 · Cited by 11
Self-citation
Metadata
- Authors
- Hardwick, N. R., Carroll, M., Kaltcheva, T., Qian, D., Lim, D., Leong, L., Chu, P., Kim, J., Chao, J., Fakih, M., Yen, Y., Espenschied, J., Ellenhorn, J. D. I., Diamond, D. J., & Chung, V.
- Affiliations
- City Of Hope National Medical Center (US)
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Diamond, Don J.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2014-09-01
- Volume
- 20
- Issue
- 17
- Pages
- 4459-4470
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC4155000
- OpenAlex
- W2045927502
- Cited by
- 45
- References
- 50
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 4 · 2020: 2 · 2018: 4 · 2017: 6 · 2016: 1 · 2015: 2 · 2014: 1
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r29ca070819-04)
- National Cancer Institute (R29 CA 70819, CA033572, R21CA114889, P30CA033572)
- National Center for Research Resources (M01RR000043)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- modified vaccinia Ankara, CD8+ T cell responses, PD-1 checkpoint, immune checkpoint blockade, vaccine immunogenicity, vaccine toxicity
- MeSH terms
- Aged, Female, Gastrointestinal Neoplasms, Humans, Male, Middle Aged, Mutation, CD4-Positive T-Lymphocytes, Tumor Suppressor Protein p53, CD8-Positive T-Lymphocytes, Cancer Vaccines
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
