Selected poster presentations Poster Discussion Session

52P - A novel rMVA combination immunotherapy triggers potent innate and adaptive immune responses against established tumors

Presentation Number
52P
Lecture Time
17:00 - 17:05
Speakers
  • Jose Medina (Martinsried, DE)
Session Name
Selected poster presentations
Location
Room Scene AB, Paris Marriott Rive Gauche, Paris, France
Date
05.03.2018
Time
16:50 - 17:10
Authors
  • Jose Medina (Martinsried, DE)
  • Maria Hinterberger (München, DE)
  • Marco Testori (Martinsried, DE)
  • Marlene Geiger (Martinsried, DE)
  • Raphael Giessel (Martinsried, DE)
  • Paul Chaplin (Martinsried, DE)
  • Hubertus Hochrein (Martinsried, DE)
  • Henning Lauterbach (Martinsried, DE)

Abstract

Background

Virus-based vaccines and appropriate costimulation enhance potent antigen-specific T cell immunity against cancer. In the present study we exploit both innate and adaptive immune responses triggered by a novel recombinant modified vaccinia virus Ankara (rMVA) encoding costimulatory CD40L against solid tumors in combination regimes to overcome tumor-induced resistance to immunotherapy.

Methods

Mice bearing tumors > 50 mm3 in volume were immunized intravenously and treated with monoclonal antibodies when indicated. Immune infiltrates were analyzed by flow cytometry. When indicated, immune populations were isolated to perform functional assays.

Results

Therapeutic treatment with rMVA-CD40L resulted in strong antitumor effects in unrelated established tumor models. Tumor infiltration was composed of non-exhausted, antigen-specific CD8+ T cells with proliferative capacity after rMVA-CD40L immunization. Strikingly, this antitumor effect was not entirely dependent on cross-presenting CD8α+ DC -induced CD8+ T cell expansion. Indeed, rMVA-CD40L-induced tumor control did not depend on cytosolic DNA sensor STING. Interestingly, rMVA-CD40L induced strong NK cell activation and thereby potent Antibody Dependent Cell Cytotoxicity (ADCC) against Tumor-Associated Antigen (TAA) targeting antibodies. Hence, the combination of TAA targeting antibodies and rMVA-CD40L resulted in increased therapeutic antitumor efficacy.

Conclusions

We describe a novel and translationally relevant therapeutic synergy between viral vaccination and CD40L costimulation. We connect CD40 ligation to cross-presenting CD8α+ DC -mediated expansion of non-exhausted CD8+ T cells in the tumor microenvironment. Taking advantage from intrinsic MVA-induced NK cell activation and further improved NK cell function by CD40 ligation, we show strengthened antitumor immune responses when both rMVA-CD40L-induced innate and adaptive immune mechanisms are exploited by combining immunotherapeutic regimes. This finding has a direct potential impact in clinical trials where TAA targeting antibodies are currently under evaluation.

Legal entity responsible for the study

Bavarian Nordic GmbH

Funding

Bavarian Nordic GmbH

Disclosure

J. Medina, M. Hinterberger, M. Testori, M. Geiger, R. Giessel, H. Hochrein, H. Lauterbach: Employee of Bavarian Nordic GmbH. P. Chaplin: CEO of Bavarian Nordic GmbH

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