Interleukin-2 and gene therapy in the management of acute lymphoblastic leukaemia.
The overall unfavourable prognosis of adult acute leukaemia patients has prompted the search for alternative therapeutic strategies. Probably the most sought challenge, which over the years has been met by consistent disillusion, has been immunotherapy. With little doubt the goal of stimulating the immune system of the host in the hope of controlling or eradicating residual disease following more conventional ablative regimens, remains conceptually a highly desirable approach. During the last few years an innovative strategy, based on the in vitro demonstration that IL2 is capable of inducing a previously unrecognized cytotoxic function directed against primary tumours and named LAK, has been applied with some success in solid tumour patients. Here, we shall review the pre-clinical data which indicate that IL2-based immunotherapy may be employed also in the management of patients with acute leukaemia. Clinical data which support a possible in vivo antileukaemic effect of IL2 are presented. The clinicohaematological modifications, as well as the biological modulations induced in the patients following the administration of IL2 are also discussed. In view of the recent demonstration that the IL2 gene can be successfully transduced into human neoplastic cells, we finally discuss the rationale of gene transfer approaches in an attempt to overcome some of the limitations associated with the administration of high doses of exogenous IL2.
Foa
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Dipartimento di Scienze, Biomediche e Oncologia Umana, University of Torino, Italy.
D000328:Adult; D000818:Animals; D016026:Bone Marrow Transplantation; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005240:Feasibility Studies; D005544:Forecasting; D015316:Genetic Therapy; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000009:adverse effects / Q000235:genetics / Q000627:therapeutic use*; D007942:Leukemia, Experimental / Q000628:therapy; D008213:Lymphocyte Activation; D051379:Mice; D008819:Mice, Nude; D015337:Multicenter Studies as Topic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy*; D011788:Quality of Life; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012074:Remission Induction; D014162:Transfection; D016896:Treatment Outcome
D016207:Cytokines; D007155:Immunologic Factors; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins