Recent developments and future challenges in immune checkpoint inhibitory cancer treatment

被引:27
作者
Koster, Bas D. [1 ]
de Gruijl, Tanja D. [1 ]
van den Eertwegh, Alfons J. M. [1 ]
机构
[1] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Amsterdam, Netherlands
关键词
anticytotoxic T-lymphocyte-associated protein 4; antiprogrammed death protein 1; antiprogrammed death-ligand 1; immune checkpoint inhibitors; immunotherapy; ipilimumab; nivolumab; pembrolizumab; RESISTANT PROSTATE-CANCER; LONG-TERM SAFETY; ANTI-PD-L1; ANTIBODY; CLINICAL ACTIVITY; PD-1; BLOCKADE; DOUBLE-BLIND; T-CELLS; ADVANCED MELANOMA; IPILIMUMAB; LUNG;
D O I
10.1097/CCO.0000000000000221
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose of review In this review, we focus on the recent findings and future challenges in cancer treatment with immune checkpoint inhibitors. Recent findings Major progress has been made in recent years as the first immune checkpoint inhibitors are approved by the US Food and Drug Administration for the treatment of cancer patients. Anticytotoxic T-lymphocyte-associated protein 4 and antiprogrammed death protein 1/programmed death-ligand 1 (PD-L1) monoclonal antibodies are being extensively studied in many different tumor types, often showing impressive response rates, but also a typical serious toxicity profile in the form of auto-immunity. Unfortunately, it is not yet possible to prevent or predict these immune-related adverse events. Studies on mutational load, neo-epitopes, lactate dehydrogenase, PD-L1 expression, and T-cell infiltration suggest that these markers are correlating with efficacy, but have not yet reached the status of a validated biomarker for checkpoint inhibitors. Other immune checkpoints are being investigated and new checkpoint inhibitors are on the brink of being evaluated in clinical trials. Summary The main challenge for the near future will be to predict efficacy of immune checkpoint blockade and to predict and prevent immune-related adverse events. More research should be done in order to find potential biomarkers that predict treatment response and/or toxicity; the optimal administration route, dosage, and frequency; and possible combinations of therapies that have an added or synergetic effect.
引用
收藏
页码:482 / 488
页数:7
相关论文
共 68 条
  • [1] [Anonymous], J CLIN ONCOL
  • [2] PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma
    Ansell, Stephen M.
    Lesokhin, Alexander M.
    Borrello, Ivan
    Halwani, Ahmad
    Scott, Emma C.
    Gutierrez, Martin
    Schuster, Stephen J.
    Millenson, Michael M.
    Cattry, Deepika
    Freeman, Gordon J.
    Rodig, Scott J.
    Chapuy, Bjoern
    Ligon, Azra H.
    Zhu, Lili
    Grosso, Joseph F.
    Kim, Su Young
    Timmerman, John M.
    Shipp, Margaret A.
    Armand, Philippe
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (04) : 311 - 319
  • [3] Clinical experience with ipilimumab 3 mg/kg: real-world efficacy and safety data from an expanded access programme cohort
    Ascierto, Paolo A.
    Simeone, Ester
    Sileni, Vanna Chiarion
    Pigozzo, Jacopo
    Maio, Michele
    Altomonte, Maresa
    Del Vecchio, Michele
    Di Guardo, Lorenza
    Marchetti, Paolo
    Ridolfi, Ruggero
    Cognetti, Francesco
    Testori, Alessandro
    Bernengo, Maria Grazia
    Guida, Michele
    Marconcini, Riccardo
    Mandala, Mario
    Cimminiello, Carolina
    Rinaldi, Gaetana
    Aglietta, Massimo
    Queirolo, Paola
    [J]. JOURNAL OF TRANSLATIONAL MEDICINE, 2014, 12
  • [4] Durable Responses With PD-1 Inhibition in Lung and Kidney Cancer and the Ongoing Search for Predictive Biomarkers
    Awad, Mark M.
    Hammerman, Peter S.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (18) : 1993 - U6
  • [5] Immune Checkpoint Protein Inhibition for Cancer: Preclinical Justification for CTLA-4 and PD-1 Blockade and New Combinations
    Baksh, Kathryn
    Weber, Jeffrey
    [J]. SEMINARS IN ONCOLOGY, 2015, 42 (03) : 363 - 377
  • [6] Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer
    Brahmer, Julie
    Reckamp, Karen L.
    Baas, Paul
    Crino, Lucio
    Eberhardt, Wilfried E. E.
    Poddubskaya, Elena
    Antonia, Scott
    Pluzanski, Adam
    Vokes, Everett E.
    Holgado, Esther
    Waterhouse, David
    Ready, Neal
    Gainor, Justin
    Aren Frontera, Osvaldo
    Havel, Libor
    Steins, Martin
    Garassino, Marina C.
    Aerts, Joachim G.
    Domine, Manuel
    Paz-Ares, Luis
    Reck, Martin
    Baudelet, Christine
    Harbison, Christopher T.
    Lestini, Brian
    Spigel, David R.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) : 123 - 135
  • [7] Clinical activity and biomarkers of MEDI4736, an anti-PD-L1 antibody, in patients with NSCLC.
    Brahmer, Julie R.
    Rizvi, Naiyer A.
    Lutzky, Jose
    Khleif, Samir
    Blake-Haskins, Andy
    Li, Xia
    Robbins, Paul B.
    Vasselli, Jim
    Ibrahim, Ramy A.
    Antonia, Scott Joseph
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (15)
  • [8] Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer
    Brahmer, Julie R.
    Tykodi, Scott S.
    Chow, Laura Q. M.
    Hwu, Wen-Jen
    Topalian, Suzanne L.
    Hwu, Patrick
    Drake, Charles G.
    Camacho, Luis H.
    Kauh, John
    Odunsi, Kunle
    Pitot, Henry C.
    Hamid, Omid
    Bhatia, Shailender
    Martins, Renato
    Eaton, Keith
    Chen, Shuming
    Salay, Theresa M.
    Alaparthy, Suresh
    Grosso, Joseph F.
    Korman, Alan J.
    Parker, Susan M.
    Agrawal, Shruti
    Goldberg, Stacie M.
    Pardoll, Drew M.
    Gupta, Ashok
    Wigginton, Jon M.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) : 2455 - 2465
  • [9] Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies
    Bulliard, Yannick
    Jolicoeur, Rose
    Windman, Maurice
    Rue, Sarah M.
    Ettenberg, Seth
    Knee, Deborah A.
    Wilson, Nicholas S.
    Dranoff, Glenn
    Brogdon, Jennifer L.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2013, 210 (09) : 1685 - 1693
  • [10] TIGIT and PD-1 impair tumor antigen-specific CD8+ T cells in melanoma patients
    Chauvin, Joe-Marc
    Pagliano, Ornella
    Fourcade, Julien
    Sun, Zhaojun
    Wang, Hong
    Sander, Cindy
    Kirkwood, John M.
    Chen, Tseng-hui Timothy
    Maurer, Mark
    Korman, Alan J.
    Zarour, Hassane M.
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2015, 125 (05) : 2046 - 2058