Capitini, C.M.

Romero, P.

Journal for ImmunoTherapy of Cancer

PubMed

Serveur académique lausannois

Capitini and Romero Journal for ImmunoTherapy of Cancer  (2015) 3:28 DOI 10.1186/s40425-015-0073-1COMMENTARY Open AccessJITC launches a new section: commentaryand editorialsChristian M. Capitini1* and Pedro Romero2EditorialBackgroundWe are pleased to announce the launch of a new sec-tion in the Journal for ImmunoTherapy of Cancer(JITC), the Commentary/Editorials section edited byChristian Capitini, MD of the University of Wisconsin.With all of the changes occurring in the field of im-munotherapy, we felt having a section that featuresexpert analysis and insight into the latest developmentswould be useful to our readers.So far in 2015, we have seen mounting excitementaround recent Food and Drug Administration (FDA)approvals for new immunotherapeutics for cancer. InMarch of this year, two monoclonal antibodies (mAbs)were approved. The first approval was for the PD-1pathway inhibitor nivolumab, which was approved formetastatic non-small cell lung cancer (NSCLC). Nivo-lumab was reviewed under the FDA’s priority reviewprogram. The second approval involved the anti-GD2therapy dinutuximab, which was approved for childrenwith high-risk neuroblastoma. Dinutuximab was grantedpriority review and orphan product designation, andbecame the second drug granted a rare pediatric diseasepriority review voucher. It is only the third drug in historyto receive initial approval for the treatment of a pediatriccancer.In addition, we have seen promising reports from earlyphase immunotherapy studies presented at the AmericanAssociation for Cancer Research (AACR) earlier this year.In the ever-expanding field of mAbs for cancer, the firstphase III trial comparing the PD-1 inhibitor pembrolizu-mab versus the CTLA4 inhibitor ipilimumab as first-linetherapy demonstrated that pembrolizumab was superiorin patients with metastatic melanoma according to all ofthe study endpoints [1]. Moreover, recent analyses ofwhole exome sequencing of NSCLC tumors treated withpembrolizumab shows that higher mutational burden, a* Correspondence: ccapitini@pediatrics.wisc.edu1Department of Pediatrics and Carbone Comprehensive Cancer Center,University of Wisconsin-Madison, Madison, WI, USAFull list of author information is available at the end of the article© 2015 Capitini and Romero. This is an OpenLicense (http://creativecommons.org/licenses/medium, provided the original work is propercreativecommons.org/publicdomain/zero/1.0/molecular smoking signature, higher neoantigen burdenand DNA repair pathway mutations improves efficacy [2].Perhaps these results, combined with data showing thatpresence of CD8+ T cells expressing PD-1 at the tumormargin is associated with tumor regression [3], willimprove access to anti-PD-1 therapies for these patients,especially in Europe where anti-PD-1 therapy is notcurrently available as a first-line therapy. In a phase I trialin patients with metastatic NSCLC, pembrolizumab wasfound to be safe. Remarkably in a cohort of patients withPD-L1+ tumors, the response rate was 45 % [4]. Beyondmelanoma and NSCLC, in a separate phase Ib trial,pembrolizumab was reported to be safe for patientswith malignant pleural mesothelioma. Some clinical re-sponses were reported.MPDL3280A is a PD-L1 inhibitor that was previouslyshown to induce response in metastatic bladder cancer[5]. In a phase I clinical trial, MPDL3280A was reportedto be safe and showed some durable clinical activity inpatients with metastatic triple-negative breast cancer. In aphase II, double-blind trial, the combination of ipilimu-mab and nivolumab was reported to show better objectiveclinical responses and progression-free survival than ipili-mumab alone [6] And in a phase I clinical trial, theanti-CD40 monoclonal antibody CP-870,893 was com-bined safely with the CTLA4 inhibitor tremelimumab inpatients with metastatic melanoma, with non-overlappingside effects reported as well as clinical responses. In aphase I/IIa trial, a monoclonal T cell Receptor anti-CD3scFv Fusion Protein IMCgp100 showed durable responsesin melanoma. In the field of adoptive cell therapy,chimeric antigen receptor (CAR)-modified T cells againstmesothelin were well tolerated across patients with mul-tiple tumor types. Importantly, no off-tumor, on-targettoxicity was reported.ConclusionWith the rapid expansion of mAb technologies such asantibody-drug conjugates, immunotoxins, immunocyto-kines, radiolabeled-mAb, and bispecific antibodies, andAccess article distributed under the terms of the Creative Commons Attributionby/4.0), which permits unrestricted use, distribution, and reproduction in anyly credited. The Creative Commons Public Domain Dedication waiver (http://) applies to the data made available in this article, unless otherwise stated.Capitini and Romero Journal for ImmunoTherapy of Cancer  (2015) 3:28 Page 2 of 2cell-based therapies like CAR-modified T cells, tumor-infiltrating lymphocytes (TILs), T cell receptor (TCR)-transduced T cells, natural killer cells, and dendritic cellvaccines, there will be lots to discuss in the comingmonths (and years) ahead. We at JITC share your interestand enthusiasm, and are prepared to keep you well in-formed of the progress made in the immunotherapy ofcancer.Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsCMC and PR drafted and revised the manuscript. Both authors read andapproved the manuscript.Author details1Department of Pediatrics and Carbone Comprehensive Cancer Center,University of Wisconsin-Madison, Madison, WI, USA. 2Translational TumorImmunology Group, Ludwig Cancer Research Center, University of Lausanne,Lausanne, Switzerland.Received: 28 May 2015 Accepted: 29 May 2015References1. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab inAdvanced Melanoma. N Engl J Med. 2015. [Epub ahead of print]2. Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutationallandscape determines sensitivity to PD-1 blockade in non-small cell lungcancer. Science. 2015;348(6230):124–8.3. Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces responsesby inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71.4. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the Treatment ofNon-Small-Cell Lung Cancer. N Engl J Med. 2015;372(21):2018–28.doi:10.1056/NEJMoa1501824. Epub 2015 Apr 19.5. Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leadsto clinical activity in metastatic bladder cancer. Nature. 2014;515(7528):558–62.6. Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and Ipilimumab versusIpilimumab in Untreated Melanoma. N Engl J Med. 2015;372(21):2006–17.doi:10.1056/NEJMoa1414428. Epub 2015 Apr 20.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color ﬁgure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submit

JITC launches a new section: commentary and editorials.

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JITC launches a new section: commentary and editorials.

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