Big opportunities for small molecules in immuno-oncology

被引：410

作者：

Adams, Jerry L. ^{[1
]}

Smothers, James ^{[1
]}

Srinivasan, Roopa ^{[1
]}

Hoos, Axel ^{[1
]}

机构：

[1] GlaxoSmithKline, Collegeville, PA 19426 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2015年 / 14卷 / 09期

关键词：

REGULATORY T-CELLS; HUMAN DENDRITIC CELLS; ADENYLYL-CYCLASE-VII; SUPPRESSOR-CELLS; TUMOR-GROWTH; CANCER-IMMUNOTHERAPY; IMMUNOSUPPRESSIVE ACTIVITY; ANTITUMOR IMMUNITY; EXTRACELLULAR ADENOSINE; ADOPTIVE IMMUNOTHERAPY;

D O I：

10.1038/nrd4596

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 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

The regulatory approval of ipilimumab (Yervoy) in 2011 ushered in a new era of cancer immunotherapies with durable clinical effects. Most of these breakthrough medicines are monoclonal antibodies that block protein-protein interactions between T cell checkpoint receptors and their cognate ligands. In addition, genetically engineered autologous T cell therapies have also recently demonstrated significant clinical responses in haematological cancers. Conspicuously missing from this class of therapies are traditional small-molecule drugs, which have previously served as the backbone of targeted cancer therapies. Modulating the immune system through a small-molecule approach offers several unique advantages that are complementary to, and potentially synergistic with, biologic modalities. This Review highlights immuno-oncology pathways and mechanisms that can be best or solely targeted by small-molecule medicines. Agents aimed at these mechanisms - modulation of the immune response, trafficking to the tumour microenvironment and cellular infiltration - are poised to significantly extend the scope of immuno-oncology applications and enhance the opportunities for combination with tumour-targeted agents and biologic immunotherapies.

引用

页码：603 / 622

页数：20

共 133 条

[1]

Balkwill F., Mantovani A., Inflammation and cancer: Back to Virchow?, Lancet, 357, pp. 539-545, (2001)

[2]

Coley W.B., Contribution to the knowledge of sarcoma, Ann. Surg., 14, pp. 199-220, (1891)

[3]

Cheever M.A., Higano C.S., Provenge (sipuleucel-T) in prostate cancer: The first FDA-approved therapeutic cancer vaccine, Clin. Cancer Res., 17, pp. 3520-3526, (2011)

[4]

Hoos A., Et al., Development of ipilimumab: Contribution to a new paradigm for cancer immunotherapy, Semin. Oncol., 37, pp. 533-546, (2010)

[5]

Hoos A., Britten C.M., Huber C., O'Donnell-Tormey J., A methodological framework to enhance the clinical success of cancer immunotherapy, Nat. Biotech., 29, pp. 867-870, (2011)

[6]

Poole R.M., Pembrolizumab: First global approval, Drugs, 74, pp. 1973-1981, (2014)

[7]

Wang C., Et al., In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates, Cancer Immunol. Res., 2, pp. 846-856, (2014)

[8]

Lee S., Margolin K., Cytokines in cancer immunotherapy, Cancers, 3, pp. 3856-3893, (2011)

[9]

Melero I., Et al., Therapeutic vaccines for cancer: An overview of clinical trials, Nat. Rev. Clin. Oncol., 11, pp. 509-524, (2014)

[10]

Restifo N.P., Dudley M.E., Rosenberg S.A., Adoptive immunotherapy for cancer: Harnessing the T cell response, Nat. Rev. Immunol., 12, pp. 269-281, (2012)

← 1 2 3 4 5 6 7 8 9 10 →