[Gene therapy of childhood cancers: current status and perspectives].
Despite the extraordinary successes of treatments for paediatric malignancies over the last 30 years, almost 30% of patients will remain refractory or will relapse after conventional or intensified therapeutic regimen. Even when successful, the long-term sequelae of current treatments include severe organ toxicity and secondary malignancies. It is becoming evident that cellular and gene transfer approaches can induce remissions in some paediatric tumours and may be useful adjuvants for others. The most convincing approach to date has been to induce antitumour immunity either by rendering tumour cells more immunogenic by genetic modification or by improving the effector activity of the host's immune cells. These approaches may be expected to become more successful as we learn more of the mechanisms tumor cells use to evade the immune response, and exploit gene transfer to overcome these tumor-defence mechanisms. Gene transfer may also be used to reverse the malignant process, modulate tumour invasiveness or enhance the susceptibility of tumour cells to cytotoxic drugs, but these approaches are at an earlier stage of development and are limited by vector deficiencies. As vector technology improves, and with an improved understanding of the oncogenic process we may expect these additional approaches more broadly applied and making a significant contribution to the ultimate goal of targeted therapy for paediatric malignancy.
Rousseau
Raphaël
R
Center for Cell and Gene Therapy, Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, 6621 Fannin Street, MC3-3320 Houston, TX 77030, USA. rousseau@bcm.tmc.edu
Biagi
Ettore
E
Bollard
Catherine
C
Brenner
Malcolm
M
D000951:Antigens, Neoplasm / Q000276:immunology; D002648:Child; D002869:Chromosome Aberrations; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D018014:Gene Transfer Techniques; D005819:Genetic Markers; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000628:therapy; D011355:Prodrugs / Q000378:metabolism; D013601:T-Lymphocytes / Q000637:transplantation
D000951:Antigens, Neoplasm; D005819:Genetic Markers; D011355:Prodrugs