A pilot trial of CTLA-4 blockade with human anti-CTLA-4 in patients with hormone-refractory prostate cancer
| Autor: | James P. Allison, Lawrence Fong, N. Simon Tchekmedyian, Israel Lowy, Eric J. Small, Brian I. Rini |
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| Rok vydání: | 2007 |
| Předmět: |
Oncology
Male Cancer Research medicine.medical_specialty Antineoplastic Agents Hormonal medicine.medical_treatment Ipilimumab Antineoplastic Agents Pilot Projects Adenocarcinoma Prostate cancer Pharmacokinetics Antigens CD Internal medicine medicine Humans CTLA-4 Antigen Aged business.industry Antibodies Monoclonal Prostatic Neoplasms Middle Aged Prostate-Specific Antigen medicine.disease Rash Antigens Differentiation Blockade Clinical trial CTLA-4 Drug Resistance Neoplasm Immune System Immunology Hormone therapy medicine.symptom business medicine.drug |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 13(6) |
| ISSN: | 1078-0432 |
| Popis: | Purpose: Blockade of the T-cell inhibitory receptor CTL-associated antigen-4 (CTLA-4) augments and prolongs T-cell responses and is a strategy to elicit antitumor immunity. The objectives of this pilot study were to establish the pharmacokinetic and safety profile for a single dose of 3 mg/kg of the anti-CTLA-4 antibody Ipilimumab (MDX-010, BMS-734016) and to assess if this therapy resulted in prostate-specific antigen (PSA) modulation and the development of polyclonal T-cell activation and/or clinical autoimmunity in patients with hormone-refractory prostate cancer treated with Ipilimumab. Experimental Design: Patients with metastatic hormone-refractory prostate cancer received a single 3 mg/kg i.v. dose of Ipilimumab. Serologic measures of autoimmunity were obtained, and T-cell activation was evaluated by flow cytometry. Pharmacokinetic sampling of plasma for MDX-CTLA-4, PSA measurement, and diagnostic imaging were also undertaken. Results: Fourteen patients were treated: 12 patients received a single dose of Ipilimumab, and 2 patients were re-treated with a second dose upon PSA progression. Two patients showed PSA declines of ≥50%. Treatment was well tolerated with clinical autoimmunity limited to one patient who developed grade 3 rash/pruritis requiring systemic corticosteroids. The mean ± SD Ipilimumab terminal elimination half-life was 12.5 ± 5.3 days. Conclusions: A single dose of 3 mg/kg Ipilimumab, an anti-CTLA-4 antibody, given to patients with prostate cancer is safe and does not result in significant clinical autoimmunity. PSA-modulating effects observed warrant further investigation. |
| Databáze: | OpenAIRE |
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