The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Intrapatient Dose Escalation of Anti–CTLA-4 Antibody in Patients With Metastatic Melanoma
Open accessAbstract
We previously reported our experience in treating 56 patients with metastatic melanoma using a human anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody. Durable tumor regressions were seen that correlated with the induction of autoimmune toxicities. In this study, we treated 46 additional patients using an intrapatient dose escalation schema to test whether higher doses of anti-CTLA-4 antibody would induce increased autoimmunity and concomitant tumor regression. Twenty-three patients started anti-CTLA-4 antibody administration at 3 mg/kg and 23 patients started treatment at 5 mg/kg, receiving doses every 3 weeks. Patients were dose-escalated every other dose to a maximum of 9 mg/kg or until objective clinical responses or grade III/IV autoimmune toxicity were seen. Escalating doses of antibody resulted in proportionally higher plasma concentrations. Sixteen patients (35%) experienced a grade III/IV autoimmune toxicity. Five patients (11%) achieved an objective clinical response. Two of the responses are ongoing at 13 and 16 months, respectively. Flow cytometric analysis of peripheral blood revealed significant increases in both T-cell surface markers of activation and memory phenotype. Thus, higher serum levels and prolonged administration of anti-CTLA-4 antibody resulted in a trend toward a greater incidence of grade III/IV autoimmune toxicity than previously reported, but did not seem to increase objective response rates.
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Cites
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Self-citationLymphoproliferative 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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Cited by
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F.-A., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E.-M., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,845
Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy
Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.001 · Cited by 4,229
Self-citationHaanen, J. B. A. G., Carbonnel, F., Robert, C., Kerr, K. M., Peters, S., Larkin, J., & Jordan, K. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx225 · Cited by 2,367
“However, in a dose escalation study, higher serum levels and prolonged administration of anti-CTLA4 Abs resulted in a trend toward a greater incidence of grade 3/4 autoimmune toxicity, but did not seem to increase anticancer response rates [48].”
BackgroundImmune-related adverse events with immune checkpoint blockade: a comprehensive review
Michot, J. M., Bigenwald, C., Champiat, S., Collins, M., Carbonnel, F., Postel-Vinay, S., Berdelou, A., Varga, A., Bahleda, R., Hollebecque, A., et al. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2015.11.016 · Cited by 2,127
Khoja, L., Day, D., Wei-Wu Chen, T., Siu, L. L., & Hansen, A. R. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx286 · Cited by 939
Metadata
- Authors
- Maker, A. V., Yang, J. C., Sherry, R. M., Topalian, S. L., Kammula, U. S., Royal, R. E., Hughes, M., Yellin, M. J., Haworth, L. R., Levy, C., Allen, T., Mavroukakis, S. A., Attia, P., & Rosenberg, S. A.
- Venue
- Journal of Immunotherapy
- Published
- 2006-07
- Volume
- 29
- Issue
- 4
- Pages
- 455-463
- ISSN
- 1524-9557 (ISSN-L)
- OpenAlex
- W2145308813
- Cited by
- 265
- References
- 51
- FWCI
- 9.61
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Intrapatient Dose Escalation of Anti–CTLA-4 Antibody in Patients With Metastatic Melanoma. https://app.cochat.ai/papers/10.1097/01.cji.0000208259.73167.58
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- Maker, A. V., Yang, J. C., Sherry, R. M., Topalian, S. L., Kammula, U. S., Royal, R. E., Hughes, M., Yellin, M. J., Haworth, L. R., Levy, C., Allen, T., Mavroukakis, S. A., Attia, P., & Rosenberg, S. A. (2006). Intrapatient Dose Escalation of Anti–CTLA-4 Antibody in Patients With Metastatic Melanoma. Journal of Immunotherapy. https://doi.org/10.1097/01.cji.0000208259.73167.58
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
