The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Autoimmunity Correlates With Tumor Regression in Patients With Metastatic Melanoma Treated With Anti–Cytotoxic T-Lymphocyte Antigen-4
Open accessAbstract
Purpose: Previously, we reported our experience treating 14 patients with metastatic melanoma using a fully human antibody to cytotoxic T-lymphocyte antigen-4 (anti–CTLA-4) in conjunction with peptide vaccination. We have now treated 56 patients to evaluate two different dose schedules of anti–CTLA-4 and to explore the relationship between autoimmunity and tumor regression. Patients and Methods: A total of 56 patients with progressive stage IV melanoma were enrolled onto the study. All had Karnofsky performance status ≥ 60% with no prior history of autoimmunity. Twenty-nine patients received 3 mg/kg anti–CTLA-4 every 3 weeks, whereas 27 received 3 mg/kg as their initial dose with subsequent doses reduced to 1 mg/kg every 3 weeks. In both cohorts patients received concomitant vaccination with two modified HLA-A*0201-restricted peptides from the gp100 melanoma-associated antigen, gp100:209-217(210M) and gp100:280-288(288V). Results: Two patients achieved a complete response (ongoing at 30 and 31 months, respectively) and five patients achieved a partial response (durations of 4, 6, 25+, 26+, and 34+ months, respectively), for an overall objective response rate of 13%. Tumor regression was seen in lung, liver, brain, lymph nodes, and subcutaneous sites. Of 14 patients with grade 3/4 autoimmune toxicity, five (36%) experienced a clinical response compared with only two responses in the 42 patients (5%) with no autoimmune toxicity (P = .008). There were no significant differences in response rate or toxicity between the two dose schedules. Conclusion: Administration of anti–CTLA-4 monoclonal antibody plus peptide vaccination can cause durable objective responses, which correlate with the induction of autoimmunity, in patients with metastatic melanoma.
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“patients who experienced grade 3/4 IRAEs had an improved ORR compared to those who did not experience grade 3/4 IRAEs (36% vs 5%, p = .008) [45].”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [45]
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Cites
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Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
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Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
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CTLA-4 can function as a negative regulator of T cell activation
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Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Self-citationImmune-Related Adverse Events Associated with Immune Checkpoint Blockade
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Wolchok, J. D., Hoos, A., O'Day, S. J., Weber, J. S., Hamid, O., Lebbé, C., Maio, M., Binder, M., Bohnsack, O., Nichol, G. M., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1624 · Cited by 3,214
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Metadata
- Authors
- Attia, P., Phan, G. Q., Maker, A. V., Robinson, M. R., Quezado, M. M., Yang, J. C., Sherry, R. M., Topalian, S. L., Kammula, U. S., Royal, R. E., Restifo, N. P., Haworth, L. R., Levy, C., Mavroukakis, S. A., Nichol, G., Yellin, M. J., & Rosenberg, S. A.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2005-09-01
- Volume
- 23
- Issue
- 25
- Pages
- 6043-6053
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC1473965
- OpenAlex
- W2151507811
- Cited by
- 1,012
- References
- 44
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 18 · 2023: 17 · 2022: 31 · 2021: 45 · 2020: 81 · 2019: 46 · 2018: 45 · 2017: 55 · 2016: 60 · 2015: 64 · 2014: 49 · 2013: 63 · 2012: 43
- FWCI
- 30.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 CA999999)
- National Cancer Institute (Z01BC010763)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Keywords
- metastatic melanoma, anti-CTLA-4 monoclonal antibody, CTLA-4 blockade, autoimmunity, autoimmune toxicity, tumor regression, peptide vaccination, gp100, dosing regimen, immune checkpoint inhibitors, objective response rate
- MeSH terms
- Adult, Aged, Antigens, Differentiation, Drug Administration Schedule, Female, Humans, Immunosuppressive Agents, Injections, Intravenous, Male, Melanoma, Middle Aged, Prognosis, Skin Neoplasms, Autoimmunity, Antigens, CD, Treatment Outcome, Cancer Vaccines, CTLA-4 Antigen
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