Bobisse, Bianchi, and Tanyi et al. reported the safety and efficacy of adoptive transfer of vaccine-primed, ex vivo-expanded autologous T cells in late-line ovarian cancer (OC) patients vaccinated with autologous DCs loaded with oxidized autologous whole-tumor lysate in combination with intravenous infusion of bevacizumab. ACT led to disease control in 12/17 patients at 3 months and decreases in the serum carbohydrate antigen 125 (CA-125) level by 12 weeks. The median OS was 14.2 months, compared to 6.2 months for patients with advanced OC beyond third-line chemotherapy. The number of detected ctDNA fragments for immunogenic mutations increased in response to ACT.
Contributed by Shishir Pant
ABSTRACT: We have previously shown that vaccination with tumor-pulsed dendritic cells amplifies neoantigen recognition in ovarian cancer. Here, in a phase 1 clinical study ( NCT01312376 /UPCC26810) including 19 patients, we show that such responses are further reinvigorated by subsequent adoptive transfer of vaccine-primed, ex vivo-expanded autologous peripheral blood T cells. The treatment is safe, and epitope spreading with novel neopeptide reactivities was observed after cell infusion in patients who experienced clinical benefit, suggesting reinvigoration of tumor-sculpting immunity.
Author Info: (1) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital
Author Info: (1) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (2) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. Center for Experimental Therapeutics, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (3) Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (4) Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (5) Institute of Pathology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. (6) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (7) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (8) Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (9) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (10) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (11) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (12) Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. (13) Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. Department of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. (14) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (15) Laboratory of Biostatistics, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece. (16) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. (17) SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. Bioinformatics Competence Center, cole Polytechnique Fdrale de Lausanne, Lausanne, Switzerland. (18) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. (19) Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (20) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland. (21) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (22) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. (23) Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA. (24) Laboratory of Biostatistics, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece. (25) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. Center for Experimental Therapeutics, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (26) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. (27) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland. george.coukos@chuv.ch. Center for Cell Immunotherapy, Department of Oncology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland. george.coukos@chuv.ch.
