Journal article
Systematic assessment of LCMV based vaccine vectors expressing melanocyte differentiation antigens in human in vitro assays and in mouse melanoma models.
- Flatz, Lukas Kantonsspital St.Gallen, St. Gallen, Switzerland;
- Cupovic, Jovana Kantonsspital St.Gallen, St. Gallen, Switzerland;
- Schmidt, Sarah Hookipa Pharma Inc., New York, NY;
- Onder, Lucas Kantonsspital St.Gallen, St. Gallen, Switzerland;
- Abdou, Marie Therese Kantonsspital St.Gallen, St. Gallen, Switzerland;
- Fritsche, Anna Katharina Kantonsspital St.Gallen, St. Gallen, Switzerland;
- Bonilla, Weldy University of Basel, Basel, Switzerland;
- Pop, Oltin Tiberiu Kantonsspital St.Gallen, St. Gallen, Switzerland;
- Tüting, Thomas University of Magdeburg, Magdeburg, Germany;
- Bergthaler, Andreas Center for Molecular Medicine (CeMM), Vienna, Austria;
- Orlinger, Klaus Hookipa Pharma, New York, NY;
- Bald, Tobias QIMR Berghofer Medical Research Institute, Brisbane, Australia;
- Ludewig, Burkhard Kantonsspital St.Gallen, St. Gallen, Switzerland;
- Ring, Sandra Kantonsspital St.Gallen, St. Gallen, Switzerland;
Published in:
- Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2019, vol. 37, no. 15_suppl, p. e14299-e14299
English
e14299 Background: Antibodies blocking the immune checkpoint pathways represent an important milestone in the treatment of patients with metastatic melanoma. However, individuals presenting cold tumors do usually not show a clinical benefit. New cancer vaccine approaches are needed to cover this gap. Methods: A novel replication attenuated vaccine vector based on lymphocytic choriomeningitis virus expressing full length melanocyte differentiation antigens is evaluated in mouse melanoma models and in PBMCs and T cell cultures from melanoma patients. Results: Here, we demonstrate that intratumoral but not intravenous injection of a recombinant propagating LCMV vector expressing the melanoma-associated antigen TRP2 leads to T cell-dependent eradication of established s.c. melanoma. Importantly, intratumoral vaccination shows an abscopal effect on distant lung metastasis and protects from a rechallenge with melanoma. Confocal microscopy and flow cytometry reveal that intratumoral injection of rLCMV vectors reprograms the tumor microenvironment resulting in sustained T cell fitness. In addition, we demonstrate that rLCMV vectors can efficiently transduce human antigen presenting cells. Moreover, in vitro data confirm that rLCMV efficiently induces T cells against various melanoma-associated antigens in PBMCs from melanoma patients. Conclusions: Preclinical assessment of propagating rLCMV vectors shows unique features of this cancer vaccine resulting in a profound and multistep activation of the cancer immunity cycle resulting in eradication of established melanomas in the B16F10 mouse model after one single immunization. Positive proof of principle experiments using PBMCs from melanoma patients suggest a rapid evaluation in clinical trials.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1200/jco.2019.37.15_suppl.e14299
- ISSN 0732-183X
- Persistent URL
- https://sonar.rero.ch/global/documents/224622
Statistics
Document views: 17
File downloads: