Format

Send to

Choose Destination
Sci Transl Med. 2018 Apr 11;10(436). pii: eaao5931. doi: 10.1126/scitranslmed.aao5931.

Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer.

Author information

1
Ovarian Cancer Research Center, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2
Department of Oncology, Lausanne University Hospital, Ludwig Institute for Cancer Research, University of Lausanne, Lausanne CH-1066, Switzerland.
3
Swiss Institute of Bioinformatics, Lausanne CH-1015, Switzerland.
4
Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
5
Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
6
Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
7
Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA 19104, USA.
8
Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
9
Laboratory of Biostatistics, School of Health Sciences, National and Kapodistrian, University of Athens, Athens, Greece.
10
Ovarian Cancer Research Center, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. lana.kandalaft@chuv.ch.

Abstract

We conducted a pilot clinical trial testing a personalized vaccine generated by autologous dendritic cells (DCs) pulsed with oxidized autologous whole-tumor cell lysate (OCDC), which was injected intranodally in platinum-treated, immunotherapy-naïve, recurrent ovarian cancer patients. OCDC was administered alone (cohort 1, n = 5), in combination with bevacizumab (cohort 2, n = 10), or bevacizumab plus low-dose intravenous cyclophosphamide (cohort 3, n = 10) until disease progression or vaccine exhaustion. A total of 392 vaccine doses were administered without serious adverse events. Vaccination induced T cell responses to autologous tumor antigen, which were associated with significantly prolonged survival. Vaccination also amplified T cell responses against mutated neoepitopes derived from nonsynonymous somatic tumor mutations, and this included priming of T cells against previously unrecognized neoepitopes, as well as novel T cell clones of markedly higher avidity against previously recognized neoepitopes. We conclude that the use of oxidized whole-tumor lysate DC vaccine is safe and effective in eliciting a broad antitumor immunity, including private neoantigens, and warrants further clinical testing.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center