title: Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival.
abstract: IMA901 is the first therapeutic vaccine for renal cell cancer (RCC) consisting of multiple tumor-associated peptides (TUMAPs) confirmed to be naturally presented in human cancer tissue. We treated a total of 96 human leukocyte antigen A (HLA-A)*02(+) subjects with advanced RCC with IMA901 in two consecutive studies. In the phase 1 study, the T cell responses of the patients to multiple TUMAPs were associated with better disease control and lower numbers of prevaccine forkhead box P3 (FOXP3)(+) regulatory T (T(reg)) cells. The randomized phase 2 trial showed that a single dose of cyclophosphamide reduced the number of T(reg) cells and confirmed that immune responses to multiple TUMAPs were associated with longer overall survival. Furthermore, among six predefined populations of myeloid-derived suppressor cells, two were prognostic for overall survival, and among over 300 serum biomarkers, we identified apolipoprotein A-I (APOA1) and chemokine (C-C motif) ligand 17 (CCL17) as being predictive for both immune response to IMA901 and overall survival. A randomized phase 3 study to determine the clinical benefit of treatment with IMA901 is ongoing.
authors: Immatics Biotechnologies GmbH, Tübingen, Germany.
authors: Steffen
authors: S
authors: Walter
authors: Toni
authors: T
authors: Weinschenk
authors: Arnulf
authors: A
authors: Stenzl
authors: Romuald
authors: R
authors: Zdrojowy
authors: Anna
authors: A
authors: Pluzanska
authors: Cezary
authors: C
authors: Szczylik
authors: Michael
authors: M
authors: Staehler
authors: Wolfram
authors: W
authors: Brugger
authors: Pierre-Yves
authors: PY
authors: Dietrich
authors: Regina
authors: R
authors: Mendrzyk
authors: Norbert
authors: N
authors: Hilf
authors: Oliver
authors: O
authors: Schoor
authors: Jens
authors: J
authors: Fritsche
authors: Andrea
authors: A
authors: Mahr
authors: Dominik
authors: D
authors: Maurer
authors: Verona
authors: V
authors: Vass
authors: Claudia
authors: C
authors: Trautwein
authors: Peter
authors: P
authors: Lewandrowski
authors: Christian
authors: C
authors: Flohr
authors: Heike
authors: H
authors: Pohla
authors: Janusz J
authors: JJ
authors: Stanczak
authors: Vincenzo
authors: V
authors: Bronte
authors: Susanna
authors: S
authors: Mandruzzato
authors: Tilo
authors: T
authors: Biedermann
authors: Graham
authors: G
authors: Pawelec
authors: Evelyna
authors: E
authors: Derhovanessian
authors: Hisakazu
authors: H
authors: Yamagishi
authors: Tsuneharu
authors: T
authors: Miki
authors: Fumiya
authors: F
authors: Hongo
authors: Natsuki
authors: N
authors: Takaha
authors: Kosei
authors: K
authors: Hirakawa
authors: Hiroaki
authors: H
authors: Tanaka
authors: Stefan
authors: S
authors: Stevanovic
authors: Jürgen
authors: J
authors: Frisch
authors: Andrea
authors: A
authors: Mayer-Mokler
authors: Alexandra
authors: A
authors: Kirner
authors: Hans-Georg
authors: HG
authors: Rammensee
authors: Carsten
authors: C
authors: Reinhardt
authors: Harpreet
authors: H
authors: Singh-Jasuja
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D016632:Apolipoprotein A-I / Q000097:blood; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D054414:Chemokine CCL17 / Q000097:blood; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016233:Immunotherapy, Active; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000627:therapeutic use*
chemical_list: C505693:APOA1 protein, human; D000951:Antigens, Neoplasm; D016632:Apolipoprotein A-I; D015415:Biomarkers; C106230:CCL17 protein, human; D019496:Cancer Vaccines; D054414:Chemokine CCL17; C524866:HLA-A*02 antigen; D015789:HLA-A2 Antigen; C583867:IMA901 vaccine; D007166:Immunosuppressive Agents; D022223:Vaccines, Subunit; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide