Vaccination of Renal Cell Cancer Patients With Modified Vaccinia Ankara Delivering the Tumor Antigen 5T4 (TroVax) Alone or Administered in Combination With Interferon-α (IFN-α) A Phase 2 Trial

被引:60
作者
Amato, Robert J. [1 ]
Shingler, William [3 ]
Goonewardena, Madusha [3 ]
de Belin, Jackie [3 ]
Naylor, Stuart [3 ]
Jac, Jaroslaw [2 ]
Willis, James [2 ]
Saxena, Somyata [2 ]
Hernandez-McClain, Joan [1 ]
Harrop, Richard [3 ]
机构
[1] Univ Texas Hlth Sci Ctr, Mem Hermann Canc Ctr, Houston, TX 77030 USA
[2] Methodist Hosp, Res Inst, Texas Med Ctr, Houston, TX 77030 USA
[3] Oxford BioMed UK Ltd, Medawar Ctr, Oxford, England
关键词
genitourinary cancers; other; phase; 1-3; trials; clinical immunology; cancer vaccines; laboratory correlates; ONCOFETAL ANTIGEN; CARCINOMA; INTERLEUKIN-2; EXPRESSION;
D O I
10.1097/CJI.0b013e3181ace876
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Attenuated vaccinia virus, modified vaccinia Ankara (MVA) has been engineered to deliver the tumor antigen 5T4 (TroVax). MVA-5T4 has been evaluated in an open-label phase 2 trial in metastatic renal cell cancer patients in which the vaccine was administered alone or in combination with interferon-alpha-2b (IFN-alpha). The safety, immunologic and clinical efficacy of MVA-5T4 with or without IFN-alpha was determined. Twenty-eight patients with metastatic renal cell cancer were treated with MVA-5T4 alone (13) or plus IFN-alpha (15). The 5T4-specific cellular and humoral responses were monitored throughout the Study. Clinical responses were assessed by measuring changes in tumor burden by computed tomography or magnetic resonance imaging scan. MVA-5T4 was well tolerated with 110 Serious adverse event attributed to vaccination. Of 23 intent-to-treat patients tested for immune responses postvaccination, 22 (96%) mounted 5T4-specific antibody and/or cellular responses. One patient treated with MVA-5T4 plus IFN-alpha showed a partial response for > 7 months, whereas an additional 14 patients (7 receiving MVA-5T4 Plus IFN and 7 receiving MVA-5T4 alone) showed periods of disease stabilization ranging from 1.73 to 9.60 months. Median progression free survival and overall survival for all intent-to-treat patients was 3.8 months (range: 1 to 11.47mo) and 12.1 months (range: 1 to 27 mo), respectively. MVA-5T4 administered alone or in combination with IFN-alpha was well tolerated in all patients. Despite the high frequency of 5T4-speciric immune responses, it is not possible to conclude that patients are receiving clinical benefit. The results are encouraging and warrant further investigation.
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收藏
页码:765 / 772
页数:8
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