Immunization of cancer patients with autologous cancer-derived heat shock protein gp96 preparations: a pilot study.
Heat shock protein (HSP)-peptide complexes isolated from murine cancers elicit protective immunity and T lymphocytes specific for the cancer from which the HSPs are isolated. A pilot study was designed to test the feasibility, immunogenicity and toxicity of such treatment in cancer patients. Sixteen patients with assorted advanced malignancies, which had become refractory to established therapies, were recruited. The gp96 vaccine was prepared for each patient from tumor obtained from that patient. Anti-tumor immune responses were evaluated using Elispot assays of T cells in peripheral blood after minimal in vitro stimulation. No unacceptable vaccine-related toxicities or auto-immune reactions were observed. Immunization with autologous gp96 elicited MHC I-restricted, tumor-specific CD8(+) T lymphocytes in 6/12 patients immunized. In addition, expansion of the NK cell population was seen in 8/13 of patients immunized. These observations are entirely consistent with the murine experience and form a firm basis for future trials with clinical end points, using autologous, patient-specific HSP-peptide vaccines.
Janetzki
S
S
IV Medizinische Klinik der Charitè, Humboldt-Universität zu Berlin, Berlin, Germany.
Palla
D
D
Rosenhauer
V
V
Lochs
H
H
Lewis
J J
JJ
Srivastava
P K
PK
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D010865:Pilot Projects; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; C052646:sarcoma glycoprotein gp96 rejection antigens