Induction of leukemia-specific antibodies by immunotherapy with leukemia-cell-derived heat shock protein 70

• Published in: Cancer science Vol. 99; no. 7; pp. 1427 - 1434
• Main Authors: Jimbo, Junko, Sato, Kazuya, Hosoki, Takaaki, Shindo, Motohiro, Ikuta, Katsuya, Torimoto, Yoshihiro, Kohgo, Yutaka
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.07.2008; Blackwell
• Subjects: Animals; Antibodies, Neoplasm - blood; Biological and medical sciences; Cancer Vaccines - immunology; CD4-Positive T-Lymphocytes - immunology; Cytotoxicity, Immunologic; Enzyme-Linked Immunosorbent Assay; Female; Hematologic and hematopoietic diseases; HSP70 Heat-Shock Proteins - immunology; Immunization; Immunoglobulin G - blood; Interleukin-4 - biosynthesis; Leukemia - immunology; Leukemia - therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Mice; Mice, Inbred BALB C; Original; Tumors; Cancerology; Antibody; Leukemia; Heat shock protein; Heat shock protein 70; Malignant hemopathy; Cancer; Cell immunotherapy
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/j.1349-7006.2008.00829.x

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. (Cancer Sci 2008; 99: 1427–1434)