Advanced Targeted, Cell and Gene-therapy Approaches for Pediatric Hematological Malignancies: Results and Future Perspectives

Overview

Journal Front Oncol

Specialty Oncology

Date 2013 May 4

PMID 23641364

Citations 3

Authors

Chiara F Magnani

Sarah Tettamanti

Francesca Maltese

Nice Turazzi

Andrea Biondi

Ettore Biagi

Affiliations

Soon will be listed here.

Abstract

Despite the survival of pediatric patients affected by hematological malignancies being improved in the last 20 years by chemotherapy and hematopoietic stem cell transplantation, a significant amount of patients still relapses. Treatment intensification is limited by toxic side effects and is constrained by the plateau of efficacy, while the pipeline of new chemotherapeutic drugs is running short. Therefore, novel therapeutic strategies are essential and researchers around the world are testing in clinical trials immune and gene-therapy approaches as second-line treatments. The aim of this review is to give a glance at these novel promising strategies of advanced medicine in the field of pediatric leukemias. Results from clinical protocols using new targeted "smart" drugs, immunotherapy, and gene therapy are summarized, and important considerations regarding the combination of these novel approaches with standard treatments to promote safe and long-term cure are discussed.

Citing Articles

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update.

Moaveni A, Amiri M, Shademan B, Farhadi A, Behroozi J, Nourazarian A Front Mol Biosci. 2024; 11:1382190.

PMID: 38836106 PMC: 11149429. DOI: 10.3389/fmolb.2024.1382190.

Immunotherapy of acute leukemia by chimeric antigen receptor-modified lymphocytes using an improved Sleeping Beauty transposon platform.

Magnani C, Turazzi N, Benedicenti F, Calabria A, Tenderini E, Tettamanti S Oncotarget. 2016; 7(32):51581-51597.

PMID: 27323395 PMC: 5239498. DOI: 10.18632/oncotarget.9955.

Antibody therapy for pediatric leukemia.

Vedi A, Ziegler D Front Oncol. 2014; 4:82.

PMID: 24795859 PMC: 4000992. DOI: 10.3389/fonc.2014.00082.

References

Aplenc R, Blaney S, Strauss L, Balis F, Shusterman S, Ingle A . Pediatric phase I trial and pharmacokinetic study of dasatinib: a report from the children's oncology group phase I consortium. J Clin Oncol. 2011; 29(7):839-44. PMC: 3068059. DOI: 10.1200/JCO.2010.30.7231. View

Villanueva M . Targeted therapies: Smart tumor, smarter treatment. Nat Rev Clin Oncol. 2012; 9(3):127. DOI: 10.1038/nrclinonc.2012.4. View

Rosenberg S, Spiess P, Lafreniere R . A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986; 233(4770):1318-21. DOI: 10.1126/science.3489291. View

Dworzak M, Schumich A, Printz D, Potschger U, Husak Z, Attarbaschi A . CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy. Blood. 2008; 112(10):3982-8. PMC: 2581996. DOI: 10.1182/blood-2008-06-164129. View

May C, Sapra P, Gerber H . Advances in bispecific biotherapeutics for the treatment of cancer. Biochem Pharmacol. 2012; 84(9):1105-12. DOI: 10.1016/j.bcp.2012.07.011. View

Griffin T, Weitzman S, Weinstein H, Chang M, Cairo M, Hutchison R . A study of rituximab and ifosfamide, carboplatin, and etoposide chemotherapy in children with recurrent/refractory B-cell (CD20+) non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2008; 52(2):177-81. PMC: 2728935. DOI: 10.1002/pbc.21753. View

Morgan R, Dudley M, Wunderlich J, Hughes M, Yang J, Sherry R . Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006; 314(5796):126-9. PMC: 2267026. DOI: 10.1126/science.1129003. View

Grupp S, Kalos M, Barrett D, Aplenc R, Porter D, Rheingold S . Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013; 368(16):1509-1518. PMC: 4058440. DOI: 10.1056/NEJMoa1215134. View

Fabbro D, Ruetz S, Bodis S, Pruschy M, Csermak K, Man A . PKC412--a protein kinase inhibitor with a broad therapeutic potential. Anticancer Drug Des. 2000; 15(1):17-28. View

10.

Acharya S, Sahoo S . PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Deliv Rev. 2010; 63(3):170-83. DOI: 10.1016/j.addr.2010.10.008. View

11.

Kantarjian H, Jeha S, Gandhi V, Wess M, Faderl S . Clofarabine: past, present, and future. Leuk Lymphoma. 2007; 48(10):1922-30. DOI: 10.1080/10428190701545644. View

12.

Kebriaei P, Huls H, Jena B, Munsell M, Jackson R, Lee D . Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies. Hum Gene Ther. 2011; 23(5):444-50. PMC: 3360496. DOI: 10.1089/hum.2011.167. View

13.

Hashii Y, Sato E, Ohta H, Oka Y, Sugiyama H, Ozono K . WT1 peptide immunotherapy for cancer in children and young adults. Pediatr Blood Cancer. 2010; 55(2):352-5. DOI: 10.1002/pbc.22522. View

14.

Hashii Y, Sato-Miyashita E, Matsumura R, Kusuki S, Yoshida H, Ohta H . WT1 peptide vaccination following allogeneic stem cell transplantation in pediatric leukemic patients with high risk for relapse: successful maintenance of durable remission. Leukemia. 2011; 26(3):530-2. DOI: 10.1038/leu.2011.226. View

15.

Arora A, Scholar E . Role of tyrosine kinase inhibitors in cancer therapy. J Pharmacol Exp Ther. 2005; 315(3):971-9. DOI: 10.1124/jpet.105.084145. View

16.

Tettamanti S, Marin V, Pizzitola I, Magnani C, Giordano Attianese G, Cribioli E . Targeting of acute myeloid leukaemia by cytokine-induced killer cells redirected with a novel CD123-specific chimeric antigen receptor. Br J Haematol. 2013; 161(3):389-401. DOI: 10.1111/bjh.12282. View

17.

Pule M, Savoldo B, Myers G, Rossig C, Russell H, Dotti G . Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med. 2008; 14(11):1264-70. PMC: 2749734. DOI: 10.1038/nm.1882. View

18.

Introna M, Borleri G, Conti E, Franceschetti M, Barbui A, Broady R . Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study. Haematologica. 2007; 92(7):952-9. DOI: 10.3324/haematol.11132. View

19.

Robbins P, Morgan R, Feldman S, Yang J, Sherry R, Dudley M . Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011; 29(7):917-24. PMC: 3068063. DOI: 10.1200/JCO.2010.32.2537. View

20.

Montagna D, Maccario R, Locatelli F . Expansion of antileukaemia CTL lines and clones for adoptive cell therapy in paediatric patients given allogeneic haematopoietic stem cell transplantation. Int J Immunogenet. 2008; 35(4-5):389-93. DOI: 10.1111/j.1744-313X.2008.00797.x. View