CD40L generates immune responses in leukemia-bearing mice, an effect that is potentiated by IL-2. We studied the feasibility, safety, and immunologic efficacy of an IL-2- and CD40L-expressing recipient-derived tumor vaccine consisting of leukemic blasts admixed with skin fibroblasts transduced with adenoviral vectors encoding human IL-2 (hIL-2) and hCD40L. Ten patients (including 7 children) with high-risk acute myeloid (n = 4) or lymphoblastic (n = 6) leukemia in cytologic remission (after allogeneic stem cell transplantation [n = 9] or chemotherapy alone [n = 1]) received up to 6 subcutaneous injections of the IL-2/CD40L vaccine. None of the patients were receiving immunosuppressive drugs. No severe adverse reactions were noted. Immunization produced a 10- to 890-fold increase in the frequencies of major histocompatibility complex (MHC)-restricted T cells reactive against recipient-derived blasts. These leukemia-reactive T cells included both T-cytotoxic/T-helper 1 (Th1) and Th2 subclasses, as determined from their production of granzyme B, interferon-gamma, and interleukin-5. Two patients produced systemic IgG antibodies that bound to their blasts. Eight patients remained disease free for 27 to 62 months after treatment (5-year overall survival, 90%). Thus, even in heavily treated patients, including recipients of allogeneic stem cell transplants, recipient-derived antileukemia vaccines can induce immune responses reactive against leukemic blasts. This approach may be worthy of further study, particularly in patients with a high risk of relapse.
Rousseau, R.F., Biagi, E., Dutour, A., Yvon, E.S., Brown, M.P., Lin, T., et al. (2006). Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation. BLOOD, 107(4), 1332-1341.
Citazione: | Rousseau, R.F., Biagi, E., Dutour, A., Yvon, E.S., Brown, M.P., Lin, T., et al. (2006). Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation. BLOOD, 107(4), 1332-1341. |
Tipo: | Articolo in rivista - Articolo scientifico |
Carattere della pubblicazione: | Scientifica |
Titolo: | Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation. |
Autori: | Rousseau, RF; Biagi, E; Dutour, A; Yvon, ES; Brown, MP; Lin, T; Mei, Z; Grilley, B; Popek, E; Heslop, HE; Gee, AP; Krance, RA; Popat, U; Carrum, G; Margolin, JF; Brenner, MK |
Autori: | |
Data di pubblicazione: | 15-feb-2006 |
Lingua: | English |
Rivista: | BLOOD |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1182/blood-2005-03-1259 |
Appare nelle tipologie: | 01 - Articolo su rivista |