Preoperative CTLA-4 blockade: Tolerability and immune monitoring in the setting of a presurgical clinical trial Journal Article
| Authors: | Carthon, B. C.; Wolchok, J. D.; Yuan, J.; Kamat, A.; Ng Tang, D. S.; Sun, J.; Ku, G.; Troncoso, P.; Logothetis, C. J.; Allison, J. P.; Sharma, P. |
| Article Title: | Preoperative CTLA-4 blockade: Tolerability and immune monitoring in the setting of a presurgical clinical trial |
| Abstract: | Purpose: Cytotoxic T lymphocyte associated antigen (CTLA-4) blockade is being explored in numerous clinical trials as an immune-based therapy for different malignancies. Our group conducted the first preoperative clinical trial with the anti-CTLA-4 antibody ipilimumab in 12 patients with localized urothelial carcinoma of the bladder. Experimental Design: Six patients were treated with 3 mg/kg/dose of anti-CTLA-4 and six patients were treated with 10 mg/kg/dose of antibody. Primary end points of the study were safety and immune monitoring. Results: Most drug-related adverse events consisted of grade 1/2 toxicities. All patients had measurable immunologic pharmacodynamic effects, consisting of an increased frequency of CD4+ICOShi T cells in tumor tissues and the systemic circulation. To determine if CD4 +ICOShi T cells could be a correlative marker for clinical outcome after treatment with anti-CTLA-4, a cohort of metastatic melanoma patients was studied retrospectively for frequency of CD4+ICOS hi T cells and survival. Data from this small cohort of patients indicated that an increased frequency of CD4+ICOShi T cells, sustained over a period of 12 weeks of therapy, correlates with increased likelihood of clinical benefit consisting of overall survival. Conclusions: Our trial shows that anti-CTLA-4 therapy has a tolerable safety profile in the presurgical setting and that a preoperative model can be used to obtain biological data on human immune responses, which can efficiently guide the monitoring of patients treated in the metastatic disease setting. ©2010 AACR. |
| Keywords: | immunohistochemistry; adult; cancer survival; clinical article; controlled study; treatment outcome; aged; middle aged; human cell; overall survival; clinical trial; diarrhea; drug safety; side effect; antineoplastic agents; cancer patient; neoadjuvant therapy; flow cytometry; forkhead transcription factors; phenotype; ipilimumab; cancer immunotherapy; melanoma; tumor markers, biological; cohort analysis; patient monitoring; retrospective study; urinary bladder neoplasms; aminotransferase blood level; aspartate aminotransferase blood level; rash; aspartate aminotransferase; antibodies, monoclonal; preoperative period; immune response; immunotherapy; cd4+ t lymphocyte; cd4-positive t-lymphocytes; urogenital surgical procedures; immunophenotyping; epididymitis; orchitis; t-lymphocyte subsets; cd4 antigen; antigens, cd; aminotransferase; cytotoxic t lymphocyte antigen 4; carcinoma, transitional cell; bladder carcinoma; amylase blood level; triacylglycerol lipase blood level; cell separation; scrotal swelling; systemic circulation; amylase; triacylglycerol lipase; uveitis; antigens, differentiation, t-lymphocyte; optic neuritis; papillitis |
| Journal Title: | Clinical Cancer Research |
| Volume: | 16 |
| Issue: | 10 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2010-05-15 |
| Start Page: | 2861 |
| End Page: | 2871 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-10-0569 |
| PUBMED: | 20460488 |
| PROVIDER: | scopus |
| PMCID: | PMC2919850 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 20 April 2011" - "CODEN: CCREF" - "Source: Scopus" |
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