title: Individualized vaccination of AML patients in remission is associated with induction of antileukemia immunity and prolonged remissions.
abstract: We developed a personalized cancer vaccine in which patient-derived acute myeloid leukemia (AML) cells are fused with autologous dendritic cells, generating a hybridoma that potently stimulates broad antitumor responses. We report results obtained from the first 17 AML patients, who achieved remission after chemotherapy and were then serially vaccinated to target minimal residual disease and prevent relapse. Vaccination was well tolerated and induced inflammatory responses at the site of administration, characterized by the dense infiltration of T cells. Vaccination was also associated with a marked rise in circulating T cells recognizing whole AML cells and leukemia-specific antigens that persisted for more than 6 months. Twelve of 17 vaccinated patients (71%; 90% confidence interval, 52 to 89%) remain alive without recurrence at a median follow-up of 57 months. The results demonstrate that personalized vaccination of AML patients in remission induces the expansion of leukemia-specific T cells and may be protective against disease relapse.
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. jrosenb1@bidmc.harvard.edu.
authors.forename: Jacalyn
authors.initials: J
authors.lastname: Rosenblatt
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Lynne
authors.initials: L
authors.lastname: Uhl
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Robin
authors.initials: R
authors.lastname: Joyce
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Levine
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Arnason
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: McMasters
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Katarina
authors.initials: K
authors.lastname: Luptakova
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Salvia
authors.initials: S
authors.lastname: Jain
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Zwicker
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Ayad
authors.initials: A
authors.lastname: Hamdan
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Boussiotis
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Steensma
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DeAngelo
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Ilene
authors.initials: I
authors.lastname: Galinsky
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Poorvi Somaiya
authors.initials: PS
authors.lastname: Dutt
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Logan
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Mary Paty
authors.initials: MP
authors.lastname: Bryant
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Dina
authors.initials: D
authors.lastname: Stroopinsky
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Lillian
authors.initials: L
authors.lastname: Werner
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Palmer
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Coll
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Washington
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Leandra
authors.initials: L
authors.lastname: Cole
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Kufe
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: David
authors.initials: D
authors.lastname: Avigan
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D006801:Humans; D007107:Immune System; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D012074:Remission Induction; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019496:Cancer Vaccines