Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis
Open accessAbstract
The inhibitory receptor CTLA4 has a key role in peripheral tolerance of T cells for both normal and tumor-associated antigens. Murine experiments suggested that blockade of CTLA4 might have antitumor activity and a clinical experience with the blocking antibody ipilimumab in patients with metastatic melanoma did show durable tumor regressions in some patients. Therefore, a phase II study of ipilimumab was conducted in patients with metastatic renal cell cancer with a primary end point of response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Two sequential cohorts received either 3 mg/kg followed by 1 mg/kg or all doses at 3 mg/kg every 3 weeks (with no intention of comparing cohort response rates). Major toxicities were enteritis and endocrine deficiencies of presumed autoimmune origin. One of 21 patients receiving the lower dose had a partial response. Five of 40 patients at the higher dose had partial responses (95% confidence interval for cohort response rate 4% to 27%) and responses were seen in patients who had previously not responded to IL-2. Thirty-three percent of patients experienced a grade III or IV immune-mediated toxicity. There was a highly significant association between autoimmune events (AEs) and tumor regression (response rate=30% with AE, 0% without AE). CTLA4 blockade with ipilimumab induces cancer regression in some patients with metastatic clear cell renal cancer, even if they have not responded to other immunotherapies. These regressions are highly associated with other immune-mediated events of presumed autoimmune origin by mechanisms as yet undefined.
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First successes of immune therapy have proved that the patient's own immune system can be activated to destroy tumor cells.
“First successes of immune therapy have proved that the patient's own immune system can be activated to destroy tumor cells [86][87][88][89][90][91][92].”
From Cancer-on-chip models for metastasis: importance of the tumor microenvironment (2024) · cites this paper as [86]
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- Authors
- Yang, J. C., Hughes, M., Kammula, U., Royal, R., Sherry, R. M., Topalian, S. L., Suri, K. B., Levy, C., Allen, T., Mavroukakis, S., Lowy, I., White, D. E., & Rosenberg, S. A.
- Affiliations
- National Institutes of Health (US)
- National Cancer Institute (US)
- Corresponding author
- Yang, James C.
- Hughes, Marybeth
- Kammula, Udai
- Royal, Richard
- Sherry, Richard M.
- Topalian, Suzanne L.
- Suri, Kimberly B.
- Levy, Catherine
- Allen, Tamika
- Mavroukakis, Sharon
- White, Donald E.
- Rosenberg, Steven A.
- ORCID
- Venue
- Journal of Immunotherapy
- Published
- 2007-11
- Volume
- 30
- Issue
- 8
- Pages
- 825-830
- ISSN
- 1524-9557 (ISSN-L)
- PMC
- PMC2134980
- OpenAlex
- W2130826590
- Cited by
- 697
- References
- 24
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 14 · 2023: 19 · 2022: 30 · 2021: 38 · 2020: 48 · 2019: 43 · 2018: 45 · 2017: 72 · 2016: 72 · 2015: 81 · 2014: 54 · 2013: 39 · 2012: 29
- FWCI
- 8.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Immunotherapy (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (Z01SC003811)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- ipilimumab, CTLA-4 blockade, metastatic renal cell carcinoma, clear cell renal cell carcinoma, tumor regression, immune-related adverse events, enteritis, hypophysitis, immune checkpoint inhibitors, antitumor immunity
- MeSH terms
- Ipilimumab, Adrenal Insufficiency, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Agents, Bone Neoplasms, Carcinoma, Renal Cell, Colitis, Duodenitis, Enteritis, Female, Humans, Hypopituitarism, Kidney Neoplasms, Liver Neoplasms, Lung Neoplasms, Male, Meningitis, Aseptic, Middle Aged, Pituitary Diseases, Treatment Outcome
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