Current Approaches in Cancer Immunotherapy


Authors: P. Otáhal ;  M. Trněný
Authors‘ workplace: I. interní klinika –  klinika hematologie 1. LF UK a VFN v Praze
Published in: Klin Onkol 2015; 28(Supplementum 3): 105-111
doi: 10.14735/amko20153S105

Overview

Methods of cancer immunotherapy have finally entered clinical medicine after years of preclinical research. Currently, there are several methods, which have proven to be very effective even in cases of incurable cancer. Antitumor monoclonal antibodies are among major therapeutic anti‑cancer drugs and have been successfully used for many ears. Novel group of antibodies are immunomodulatory antibodies which can break tumor‑ specific immune tolerance and induce regression of tumors by non‑specific activation of immune system. Bispecific antibodies represent a novel class of anti‑cancer agents which can induce expansion of T cells in vivo, blinatumomab is an example of such agents and is currently available for the treatment of acute B‑ cell leukemia. Cellular immunotherapy is also very effective, especially the use of Chimeric receptor modified T-cells for the therapy of B‑ cell lymphoproliferative diseases. Although it is a very complicated and expensive method, it is highly effective approach which can induce remission even in previously hopeless conditions. The goal of this article is to explain the basic principles of cancer immunotherapy and summarize the newest findings in this field.

Key words:
cancer – lymphoma – immunotherapy – monoclonal antibodies – gene therapy

This study was supported by grant of Internal Grant Agency of the Czech Ministry of Health No. NT/14030-3.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
23. 9. 2015

Accepted:
27. 9. 2015


Sources

1. Ansel­l SM. Target­ing im­mune checkpoints in lymphoma. Cur­r Opin Hematol 2015; 22(4): 337– 342. doi: 10.1097/ MOH.0000000000000158.

2. Joyce JA, Fearon DT. T cel­l exclusion, im­mune privilege, and the tumor microenvironment. Science 2015; 348(6230): 74– 80. doi: 10.1126/ science.aaa6204.

3. Sim GC, Martin‑Orozco N, Jin L et al. IL‑2 therapy promotes suppres­sive ICOS+ Treg expansion in melanoma patients. J Clin Invest 2014; 124(1): 99– 110.

4. Suresh T, Lee LX, Joshi J et al. New antibody approaches to lymphoma therapy. J Hematol Oncol 2014; 7: 58. doi: 10.1186/ s13045‑ 014‑ 0058‑ 4.

5. van Oers MH et al. Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukaemia (PROLONG): an open‑ label, multicentre, randomized phase 3 study. Lancet Oncol 2015.

6. Goede V, Fischer K, Busch R et al. Obinutuzumab plus chlorambucil in patients with CL­l and coexist­ing conditions. N Engl J Med 2014; 370(12): 1101– 1110. doi: 10.1056/ NEJMoa1313984.

7. Sheridan C. Amgen‘s bispecific antibody puf­fs acros­s finish line. Nat Biotechnol 2015; 33(3): 219– 221. doi: 10.1038/ nbt0315‑ 219.

8. Topp MS, Gökbuget N, Zugmaier G et al. Phase II trial of the anti‑CD19 bispecific T cel­l‑ engager blinatumomab shows hematologic and molecular remis­sions in patients with relapsed or refractory B‑ precursor acute lympho­blastic leukemia. J Clin Oncol 2014; 32(36): 4134– 4140. doi: 10.1200/ JCO.2014.56.3247.

9. Bargou R, Leo E, Zugmaier G et al. Tumor regres­sion in cancer patients by very low doses of a T cel­l‑ engag­ing antibody. Science 2008; 321(5891): 974– 977. doi: 10.1126/ science.1158545.

10. Rothe A, Sas­se S, Topp MS et al. A phase 1 study of the bispecific anti‑CD30/ CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Blood 2015; 125(26): 4024– 4031. doi: 10.1182/ blood‑ 2014‑ 12‑ 614636.

11. Sun L­l, El­lerman D, Mathieu M et al. Anti‑CD20/ CD3 T cel­l‑ dependent bispecific antibody for the treatment of B cel­l malignancies. Sci Transl Med 2015; 7(287): 287ra70. doi: 10.1126/ scitranslmed.aaa4802.

12. Eyre TA, Col­lins GP. Im­mune checkpoint inhibition in lymphoid disease. Br J Haematol 2015; 170(3): 291– 304. doi: 10.1111/ bjh.13397.

13. Mahoney KM, Ren­nert PD, Freeman GJ. Combination cancer im­munotherapy and new im­munomodulatory targets. Nat Rev Drug Discov 2015; 14(8): 561– 584. doi: 10.1038/ nrd4591.

14. Valsecchi ME. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015; 373(13): 1270. doi: 10.1056/ NEJMc1509660#SA1.

15. Calabrò L, Mor­ra A, Fonsatti E et al. Ef­ficacy and safety of an intensified schedule of tremelimumab for chemotherapy‑resistant malignant mesothelioma: an open‑ label, single‑arm, phase 2 study. Lancet Respir Med 2015; 3(4): 301– 309. doi: 10.1016/ S2213‑ 2600(15)00092‑ 2.

16. Ansel­l SM, Lesokhin AM, Bor­rel­lo I. PD‑ 1 blockade with nivolumab in relapsed or refractory Hodgkin‘s lymphoma. N Engl J Med 2015; 372(4): 311– 319. doi: 10.1056/ NEJMoa1411087.

17. Moskowitz CH, Ribrag V, Michot JM et al. PD‑ 1 Block­ade with the monoclonal antibody pembrolizumab (MK‑ 3475) in patients with clas­sical Hodgkin lymphoma after brentuximab vedotin failure: preliminary results from a phase 1b study (KEYNOTE‑ 013). Blood 2014; 124(21): 290.

18. Westin JR, Chu F, Zhang M et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed fol­licular lymphoma: a single group, open‑ label, phase 2 trial. Lancet Oncol 2014; 15(1): 69– 77. doi: 10.1016/ S1470‑ 2045(13)70551‑ 5.

19. Tanimoto T, Hori A, Kami M. Sipuleucel‑ T im­muno­therapy for castration‑resistant prostate cancer. N Engl J Med 2010; 363(20): 1966; author reply 1967– 1968. doi: 10.1056/ NEJMc1009982#SA1.

20. Huber ML, Haynes L, Parker C et al. Interdisciplinary critique of sipuleucel‑ T as im­munotherapy in castration‑resistant prostate cancer. J Natl Cancer Inst 2012; 104(4): 273– 279. doi: 10.1093/ jnci/ djr514.

21. Schuster SJ, Neelapu SS, Gause BL et al. Vaccination with patient‑ specific tumor‑ derived antigen in first remis­sion improves disease‑free survival in fol­licular lymphoma. J Clin Oncol 2011; 29(20): 2787– 2794. doi: 10.1200/ JCO.2010.33.3005.

22. Porter DL, Hwang WT, Frey NV et al. Chimeric antigen receptor T cel­ls persist and induce sustained remis­sions in relaps­ed refractory chronic lymphocytic leukemia. Sci Transl Med 2015; 7(303): 303ra139. doi: 10.1126/ scitranslmed.aac5415.

23. Maude SL, Teachey DT1, Porter DL et al. CD19- target­­ed chimeric antigen receptor T‑ cel­l therapy for acute lymphoblastic leukemia. Blood 2015; 125(26): 4017– 4023. doi: 10.1182/ blood‑ 2014‑ 12‑ 580068.

24. Kochenderfer JN, Dudley ME, Kas­sim SH et al. Chemotherapy‑ refractory dif­fuse large B‑ cel­l lymphoma and indolent B‑ cel­l malignancies can be ef­fectively treated with autologous T cel­ls expres­s­ing an anti‑CD19 chimeric antigen receptor. J Clin Oncol 2015; 33(6): 540– 549. doi: 10.1200/ JCO.2014.56.2025.

25. Klebanof­f CA, Yamamoto TN, Restifo NP. Im­munotherapy: treatment of aggres­sive lymphomas with anti‑CD19 CAR T cel­ls. Nat Rev Clin Oncol 2014; 11(12): 685– 686. doi: 10.1038/ nrclinonc.2014.190.

26. Mardiros A, Dos Santos C, McDonald T. T cel­ls expres­s­ing CD123- specific chimeric antigen receptors exhibit specific cytolytic ef­fector functions and antitumor ef­fects against human acute myeloid leukemia. Blood 2013; 122(18): 3138– 3148. doi: 10.1182/ blood‑ 2012‑ 12‑ 474056.

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Paediatric clinical oncology Surgery Clinical oncology
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