Induction of leukemia-specific antibodies by immunotherapy with leukemia-cell-derived heat shock protein 70.
Cancer immunotherapy using heat shock protein (HSP) derived from autologous tumor requires cluster of differentiation (CD)4(+) as well as CD8(+) T-cells for the prolongation of patient survival, suggesting that a humoral immune response through CD4(+) T-cells is important in addition to cellular immunity. However, the role of humoral responses in HSP-based autologous tumor immunotherapy remains unclear. In the present study, we investigated whether leukemia-specific antibodies and antibody-mediated cytotoxicity against autologous leukemia cells have a crucial role in a mouse A20 leukemia model by immunizing A20-derived HSP70. Immunization with A20-derived HSP70 induced the production of anti-A20-antibodies and the antibodies recognized HSP70-binding peptides derived from A20. One of those was a major histocompatibility complex (MHC) class-I binding peptide, which has been clarified as the target peptide of CD8+ cytotoxic T-cells (CTL) against A20. The anti-A20-antibodies produced by immunization with A20-derived HSP70 induced complement-dependent cytotoxicity (CDC) against A20 in vitro. In addition, immunization with A20-derived HSP70 increased intracellular interleukin-4 (IL4)-production of CD4(+) T-cells, confirming the activation of type-2 helper T-cells. Taken together, immunization with leukemia-cell-derived HSP70 induces antibodies against leukemia-cell-specific peptides and might play a crucial role in the eradication of leukemia cells by CDC in mice. These findings will enable future establishment of a novel therapeutic strategy using antileukemia antibodies in HSP-based autologous tumor immunotherapy.
Jimbo
Junko
J
Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical College, Asahikawa, Japan.
Sato
Kazuya
K
Hosoki
Takaaki
T
Shindo
Motohiro
M
Ikuta
Katsuya
K
Torimoto
Yoshihiro
Y
Kohgo
Yutaka
Y
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D007074:Immunoglobulin G; D015847:Interleukin-4