Immunotherapy using heat-shock protein preparations of leukemia cells after syngeneic bone marrow transplantation in mice

Citation
K. Sato et al., Immunotherapy using heat-shock protein preparations of leukemia cells after syngeneic bone marrow transplantation in mice, BLOOD, 98(6), 2001, pp. 1852-1857
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
0006-4971 → ACNP
Volume
98
Issue
6
Year of publication
2001
Pages
1852 - 1857
Database
ISI
SICI code
0006-4971(20010915)98:6<1852:IUHPPO>2.0.ZU;2-N
Abstract
Heat-shock proteins (HSPs) act as molecular chaperones binding endogenous a ntigenic peptides and transporting them to major histocompatibility complex es. HSPs chaperone a broad repertoire of endogenous peptides including tumo r antigens. For the immunotherapy of tumors, a strategy using HSPs may be m ore advantageous than other procedures because the identification of each t umor-specific antigen is not necessary. In this study, the efficacy of immu notherapy against minimal residual leukemia cells using HSP preparations wa s evaluated. HSP70 and GP96 were purified from syngeneic leukemia cell line A20 and immunized into BALB/c mice during the reconstitution period of the immune system after syngeneic bone marrow transplantation. In this procedu re, all mice not immunized were dead within 60 days of A20 inoculation, whe reas the survival times of HSP-immunized mice were significantly prolonged. In addition, the depletion of either CD4(+) or CD8(+) T lymphocyte signifi cantly abrogated this efficacy, Indicating that both CD4(+) and CD8(+) T ly mphocytes were required for tumor cell rejection. Moreover, the vaccination of HSPs elicited a specific response of potent CD8(+) T lymphocytes cytoto xic against A20 in vitro. These observations suggest that immunization of t he complex of HSPs and peptides derived from leukemia cells leads to immune responses. These immune responses are sufficient to reject minimal amounts of leukemia cells for relatively immunocompromised mice after syngeneic bo ne marrow transplantation.