IMA901: A multi-peptide cancer vaccine for treatment of renal cell cancer

被引:42
作者
Kirner, Alexandra [1 ]
Mayer-Mokler, Andrea [1 ]
Reinhardt, Carsten [1 ]
机构
[1] Immat Biotechnol GmbH, Tubingen, Germany
关键词
Cancer vaccine; checkpoint inhibitor; cyclophosphamide; GM-CSF; IMA901; immunotherapy; kidney cancer; renal cell carcinoma; tumor-associated peptides; vaccination; g; Microgram; 5-FU; 5; fluorouracil; AE; Adverse event; ccRCC; Clear cell renal cell carcinoma; CTL; Cytotoxic T-lymphocyte; CY; Cyclophosphamide; DC; Dendritic cell; DCR; Disease control rate; ECG; Electrocardiogram; ELISpot; Enzyme-linked immunospot assay; FDA; Food and Drug Administration; HBV; Hepatitis B virus; HLA; Human leukocyte antigen; i; d; intradermal; intradermally; IFN; Interferon; IL; Interleukin; mg; Milligram; MHC; Major histocompatibility complex; mRNA; Messenger ribonucleic acid; MDSC; Myeloid-derived suppressor cells; MSKCC; Memorial Sloan Kettering Cancer Center; mTOR; Mammalian target of rapamycin; n; Number; NCI-CTC; National Cancer Institute-Common Toxicity Criteria; OS; Overall survival; PD; Progressive disease; PFS; Progression-free survival; PK; Pharmacokinetic; PR; Partial response; RCC; Renal cell carcinoma; RECIST; Response Evaluation Criteria in Solid Tumors; SAE; Serious adverse event; s; c; subcutaneous; subcutaneously; SD; Stable disease; TKI; Tyrosine-kinase inhibitors; TNF; Tumor necrosis factor; Tregs; Regulatory T-cells; TUMAP; Tumor-associated peptides; VEGF; Vascular endothelial growth factor; REGULATORY T-CELLS; PULSED DENDRITIC CELLS; GM-CSF GENE; KIDNEY CANCER; SIPULEUCEL-T; HISTOLOGIC SUBTYPES; DOUBLE-BLIND; CARCINOMA; CYCLOPHOSPHAMIDE; IMMUNOTHERAPY;
D O I
10.4161/21645515.2014.983857
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Despite a major improvement in the treatment of advanced kidney cancer by the recent introduction of targeted agents such as multi-kinase inhibitors, long-term benefits are still limited and a significant unmet medical need remains for this disease. Cancer immunotherapy has shown its potential by the induction of long-lasting responses in a small subset of patients, however, the unspecific immune interventions with (high dose) cytokines used so far are associated with significant side effects. Specific cancer immunotherapy may circumvent these problems by attacking tumor cells while sparing normal tissue with the use of multi-peptide vaccination being one of the most promising strategies. We here summarize the clinical and translational data from phase I and II trials investigating IMA901. Significant associations of clinical benefit with detectable T cell responses against the IMA901 peptides and encouraging survival data in treated patients has prompted the start of a randomized, controlled phase III trial in 1st line advanced RCC with survival results expected toward the end of 2015. Potential combination strategies with the recently discovered so-called checkpoint inhibitors are also discussed.
引用
收藏
页码:3179 / 3189
页数:11
相关论文
共 83 条
[71]   Maturing of Renal Cancer Therapeutics [J].
Stadler, Walter M. .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (08) :722-724
[72]   Therapeutic approaches in metastatic renal cell carcinoma [J].
Staehler, M ;
Rohrmann, K ;
Bachmann, A ;
Zaak, D ;
Stief, CG ;
Siebels, M .
BJU INTERNATIONAL, 2005, 95 (08) :1153-1161
[73]   Induction of IgM, IgA and IgE Antibodies in Colorectal Cancer Patients Vaccinated with a Recombinant CEA Protein [J].
Staff, Caroline ;
Magnusson, Carl G. M. ;
Hojjat-Farsangi, Mohammad ;
Mosolits, Szilvia ;
Liljefors, Maria ;
Frodin, Jan-Erik ;
Wahren, Britta ;
Mellstedt, Hakan ;
Ullenhag, Gustav J. .
JOURNAL OF CLINICAL IMMUNOLOGY, 2012, 32 (04) :855-865
[74]   Increased incidence of renal parenchymal carcinoma in the Northern and Yorkshire region of England, 1978-1997 [J].
Tate, R ;
Iddenden, R ;
Harnden, P ;
Morris, E ;
Craigs, C ;
Bennett, C ;
Brook, C ;
Haward, RA ;
Forman, D .
EUROPEAN JOURNAL OF CANCER, 2003, 39 (07) :961-967
[75]  
Therasse P, 2000, J NATL CANCER I, V92, P205, DOI 10.1093/jnci/92.3.205
[76]   Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer [J].
Topalian, Suzanne L. ;
Hodi, F. Stephen ;
Brahmer, Julie R. ;
Gettinger, Scott N. ;
Smith, David C. ;
McDermott, David F. ;
Powderly, John D. ;
Carvajal, Richard D. ;
Sosman, Jeffrey A. ;
Atkins, Michael B. ;
Leming, Philip D. ;
Spigel, David R. ;
Antonia, Scott J. ;
Horn, Leora ;
Drake, Charles G. ;
Pardoll, Drew M. ;
Chen, Lieping ;
Sharfman, William H. ;
Anders, Robert A. ;
Taube, Janis M. ;
McMiller, Tracee L. ;
Xu, Haiying ;
Korman, Alan J. ;
Jure-Kunkel, Maria ;
Agrawal, Shruti ;
McDonald, Daniel ;
Kollia, Georgia D. ;
Gupta, Ashok ;
Wigginton, Jon M. ;
Sznol, Mario .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2443-2454
[77]   Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells [J].
Turk, MJ ;
Guevara-Patiño, JA ;
Rizzuto, GA ;
Engelhorn, ME ;
Houghton, AN .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (06) :771-782
[78]   Durable carcinoembryonic antigen (CEA)-specific humoral and cellular immune responses in colorectal carcinoma patients vaccinated with recombinant CEA and granulocyte/macrophage colony-stimulating factor [J].
Ullenhag, GJ ;
Frödin, JE ;
Jeddi-Tehrani, M ;
Strigård, K ;
Eriksson, E ;
Samanci, A ;
Choudhury, A ;
Nilsson, B ;
Rossmann, ED ;
Mosolits, S ;
Mellstedt, H .
CLINICAL CANCER RESEARCH, 2004, 10 (10) :3273-3281
[79]   Racial disparity in incidence patterns and outcome of kidney cancer [J].
Vaishampayan, UN ;
Ho, H ;
Hussain, HDM ;
Schwartz, K .
UROLOGY, 2003, 62 (06) :1012-1017
[80]   Prognostic factors in metastatic renal cell carcinoma: metastasectomy as independent prognostic variable [J].
Vogl, U. M. ;
Zehetgruber, H. ;
Dominkus, M. ;
Hejna, M. ;
Zielinski, C. C. ;
Haitel, A. ;
Schmidinger, M. .
BRITISH JOURNAL OF CANCER, 2006, 95 (06) :691-698