No treatment-related deaths were observed in a US multi-center cohort of 165 patients who received axicabtagen-ciloleucel for r/r DLBCL after commercialization outside of clinical trials [81]. 2017;40(1):68-77. doi: 10.2177/jsci.40.68. In contrast to CAR T cells, tumor reactive T cells recognize tumor cells via their native (unmodified) T cell receptor (Fig. In light of this, Tauriello et al. Kruger S, Ilmer M, Kobold S, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. One small study in NSCLC patients suggested that high sPD-L1 levels predict poor response to nivolumab [57], a finding that is somewhat contrary to tissue PD-L1, because high PD-L1 tissue expression indicates higher likelihood of response to checkpoint blockade. 2016;6(12):1382–99. Alternative approaches are genetic modification of the T cell receptor (TCR) itself or the adoptive transfer of “naturally” occurring tumor reactive T cells (also termed tumor infiltrating lymphocytes or TILs) isolated from autologous tumor tissue or tumor draining lymph nodes (Fig. On the other hand, the need for symptomatic and sustained administration of steroids for other reasons (e.g. Conception of the review: SK, MI, SebK, SB and MvB. Article  A large number of clinical trials is currently investigating neoadjuvant immunotherapy for different disease entities (for example, we identified nine clinical trials for neoadjuvant anti- PD-1 / PD-L1 treatment in NSCLC: NCT03197467, NCT02938624, NCT02259621, NCT03694236, NCT03732664, NCT02994576, NCT03030131, NCT02716038, NCT02818920). The authors declare that they have no competing interests. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SAJR, Behjati S, Biankin AV, et al. In this regard, it is important to note, that the combination of two immunomodulatory drugs can also have antagonistic instead of synergistic effects [26]. Rosenberg SA, Restifo NP. 2018;6(1):8. While the mentioned results are reassuring regarding saftey of CAR T cell therapy, different strategies are currently under investigation to further improve the safety profile of CAR T cells. New treatments and new combinations of them are giving men with advanced prostate cancer more help than ever. 2018;24(6):749–57. 2018;132(Suppl 1):95. Dahl K, Karlsson M, Marits P, Hoffstedt A, Winqvist O, Thörn M. Metinel node—the first lymph node draining a metastasis—contains tumor-reactive lymphocytes. Neoadjuvant anti-OX40 (MEDI6469) prior to surgery in head and neck squamous cell carcinoma. Drake CG. Here is a look at some of the latest cancer research trends. Department of Medicine III, University Hospital Munich, LMU Munich, Marchioninistr. Advances in cancer immunotherapy 2019 – latest trends Stephan Kruger 1,3*† , Matthias Ilmer 2,6† , Sebastian Kobold 3 , Bruno L. Cadilha 3 , Stefan Endres 3 , Steffen Ormanns 4 , J Clin Oncol. Garcia CA, El-Ali A, Rath TJ, Contis LC, Gorantla V, Drappatz J, et al. Article  Recently, safety of axicabtagen-ciloleucel was also confirmed in patients ≥65 years [83]. Early assessment of lung Cancer immunotherapy response via circulating tumor DNA. Borchmann P, Tam CS, Jäger U, McGuirk JP, Holte H, Waller EK, et al. CAS  For checkpoint blockade, current studies focus on combinational approaches, perioperative use, new tumor entities, response prediction, toxicity management and use in special patient populations. Privacy, Help 2017;8(23):38056–60. Article  On the analogy between spontaneous recoveries from Cancer and the specific immunity induced by X ray irradiations of the lymphatic glands involved. provided an example for an elaborate pre-clinical model system. Last year saw the completion of several practice-changing phase III trials showing the efficacy of combining PD-1 / PD-L1-blockade with chemotherapy in small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), HNSCC and breast cancer [12,13,14,15]. For axicabtagen-ciloleucel, the 2-year follow-up data was presented at ASH 2018. The occurrence of immune-mediated side effects (e.g. Tang J, Shalabi A, Hubbard-Lucey VM. Ann Oncol. A response to therapy (PR or CR) was observed in 24% of patients [71]. 2018;132(Suppl 1):96. 2016;7(14):18508–20. Prospects for personalized combination immunotherapy for solid tumors based on adoptive cell therapies and immune checkpoint blockade therapies. The authors reported an ORR of 79% (50% CR), confirming the results reported in the clinical trials mentioned above [81]. Science (New York, NY). The placebo-controlled, randomized phase III PACIFIC trial investigated the addition of durvalumab (anti-PD-L1) to platinum-based chemoradiotherapy in locally advanced (stage III) NSCLC. Immunotherapy advances continue to grow, expanding to cancers where there have been few immunotherapy treatment successes to date: A new combination immunotherapy regimen was proven to boost overall survival in patients with renal cell cancer, gaining Food and Drug Administration (FDA) approval and becoming the new standard of care. Nature medicine. Advances in cancer immunotherapy 2019—latest trends. One possibility for adjuvant treatment stratification might be detection of minimal residual disease (MRD) by circulating tumor DNA (ctDNA), a strategy, that is currently investigated by a clinical trial in triple-negative breast cancer (TNBC) (NCT03145961) [42]. 2012;12(4):253-68. PubMed  J Clin Oncol. 2018;24(20):4960–7. Nat Med. Stephan Kruger and Matthias Ilmer contributed equally to this work. Clin Transl Immunology. T-effector, interferon-γ and myeloid inflammatory gene expression signatures were superior to TMB in predicting response to atezolizumab [53]. 1a). 2018;36(9):847–56. Costantini A, Julie C, Dumenil C, Helias-Rodzewicz Z, Tisserand J, Dumoulin J, et al. Wise selection strategies based on pre-clinical data to select combinatorial approaches for clinical testing are important [26]. 2018;21(3):135-150. doi: 10.3923/pjbs.2018.135.150. 2021 Feb 2;10(2):e1246. Cite this article. Only about 3 percent of cancer patients in the United States enroll in a … With new breakthroughs in immunotherapy, we keep our prostate cancer information up to date. Yu G, Butler MK, Abdelmaksoud A, Pang Y, Su YT, Rae Z, Dadkhah K, Kelly MC, Song YK, Wei JS, Terabe M, Atony R, Mentges K, Theeler BJ, Penas-Prado M, Butman J, Camphausen K, Zaghloul KA, Nduom E, Quezado M, Aldape K, Armstrong TS, Gilbert MR, Gulley JL, Khan J, Wu J. Of interest and in harsh contrast to trials on PD-1 / PD-L1 blockade is the regional distribution of clinical trials on CAR T cell therapy (Fig. Re-infusion of CAR T cells is preceded by a lympho-depleting chemotherapy to allow for subsequent in vivo expansion of CAR T cells (Fig. MSI/dMMR results in increased tumor mutational burden (TMB) with subsequent increase in neoantigens and immune cell infiltration, rendering tumors susceptible to PD-1 /PD-L1 blockade [46]. Coordinated regulation of myeloid cells by tumours. In Europe, nivolumab was the first checkpoint inhibitor approved for adjuvant treatment of melanoma patients, based on results of the CheckMate 238 study reported in 2017 [36]. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Although the incidence of immune-mediated side effects was significantly increased in the group of patients with pre-existing autoimmune diseases (44% versus 23%), there was no difference in overall survival between the two groups. 2019 Jun 19;38(1):268. doi: 10.1186/s13046-019-1266-0. Advances in cancer immunotherapy 2019 – latest trends. Goldberg SB, Narayan A, Kole AJ, Decker RH, Teysir J, Carriero NJ, et al. The two main drivers behind this success are checkpoint inhibitors (CPIs) and chimeric antigen receptor (CAR) T cells. Brix N, Tiefenthaller A, Anders H, Belka C, Lauber K. Abscopal, immunological effects of radiotherapy: narrowing the gap between clinical and preclinical experiences. 2015;348(6230):124–8. PD-1 restrains radiotherapy-induced Abscopal effect. 2017;377(26):2531–44. Would you like email updates of new search results? Part of 2010;70(8):3052–61. Article  All registered trials were sorted for tumor type and country/region. Abstract S799, presented at the annual congress of the European Hematology Association (EHA) 2018. 2019;7(1):99. These strategies include: (I) modification of the chimeric antigen receptor cell itself [85, 86]; (II) identification of predictive biomarkers for CAR T cell toxicity [84]; (III) “safety switches” such as inducible suicide genes [87]; and (IV) novel drugs to mitigate CRS and NE [88]. 2016;375(19):1845–55. ... Are there immunotherapy advances that have shown promise in breast cancer? Haanen JBAG, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, et al. PubMed  1a). Article  It should be noted, that these analyses were exploratory. 2019;7(4):528–33. Bethesda, MD 20894, Copyright The importance of immunotherapy has been acknowledged by the Nobel prize for physiology or medicine 2018... Checkpoint inhibitors. Oncoimmunology. These studies, however, were not controlled for lead time bias [66] and it is therefore not clear, whether IrAEs are truly independent predictors for response or merely reflect a longer time under treatment. 2018;29(12):2348–55. 1b). 2019;5. Pembrolizumab plus chemotherapy for squamous non-small-cell lung Cancer. Careers. Translational results from an ongoing phase I/II trial (NCT01976585) investigating local radiotherapy in combination with local application of immunostimulatory agents in patients with indolent lymphoma further support the combination of radiotherapy and PD-1 / PD-L1 blockade [21]. This leads to immune stimulatory signals via activation of the innate immune system through pattern recognition receptors such as toll-like receptor 4 (TLR4) [5]. Kadia TM, Cortes JE, Ghorab A, Ravandi F, Jabbour E, Daver NG, et al. This finding was confirmed and put into therapeutic context by the ChekMate227 trial [52]. N Engl J Med. With that background, two remarkable studies from 2018 should be mentioned here in more detail. TMB measured in peripheral blood has been shown to predict response to checkpoint blockade in NSCLC patients [58, 59]. Chimeric antigen receptor T cells (CAR T cells); Immunotherapy; Programmed cell death protein 1 (PD-1); Programmed cell death protein ligand 1 (PD-L1); Regional distribution; Trends. Epub 2017 Sep 14. Lee JH, Long GV, Boyd S, Lo S, Menzies AM, Tembe V, et al. Hellmann MD, Ciuleanu T-E, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, et al. Neurologic immune-related adverse events associated with adjuvant ipilimumab: report of two cases. Sano D, Nastoupil LJ, Fowler NH, Fayad L, Hagemeister FB, Lee HJ, et al. Disruption of this axis by blocking monoclonal antibodies can induce durable remissions in different cancer types and has led to numerous FDA and EMA approvals, among others, for the treatment of melanoma, lung cancer, urothelial cancer, head and neck squamous cell carcinoma (HNSCC), renal cell cancer (RCC) and Hodgkin’s disease [3]. McDermott DF, Huseni MA, Atkins MB, Motzer RJ, Rini BI, Escudier B, et al. In different studies, the direct determination of TMB was also established as predictive biomarker for immunotherapy [47,48,49]. PubMed  Share this article via email with one or more people using the form below. CAS  The 2020–2021 Advances in Cancer Immunotherapy ™ educational series is supported, in part, by independent medical education grants from Amgen, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Exelixis, Inc., and Merck & Co., Inc. Recently published studies suggest that changes in ctDNA levels can also be early predictors for response to immunotherapy [61, 62].