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mRNA Cancer Vaccines

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Current Strategies in Cancer Gene Therapy

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 209))

Abstract

mRNA cancer vaccines are a relatively new class of vaccines, which combine the potential of mRNA to encode for almost any protein with an excellent safety profile and a flexible production process. The most straightforward use of mRNA vaccines in oncologic settings is the immunization of patients with mRNA vaccines encoding tumor-associated antigens (TAAs). This is exemplified by the RNActive® technology, which induces balanced humoral and cellular immune responses in animal models and is currently evaluated in several clinical trials for oncologic indications. A second application of mRNA vaccines is the production of personalized vaccines. This is possible because mRNA vaccines are produced by a generic process, which can be used to quickly produce mRNA vaccines targeting patient-specific neoantigens that are identified by analyzing the tumor exome. Apart from being used directly to vaccinate patients, mRNAs can also be used in cellular therapies to transfect patient-derived cells in vitro and infuse the manipulated cells back into the patient. One such application is the transfection of patient-derived dendritic cells (DCs) with mRNAs encoding TAAs, which leads to the presentation of TAA-derived peptides on the DCs and an activation of antigen-specific T cells in vivo. A second application is the transfection of patient-derived T cells with mRNAs encoding chimeric antigen receptors, which allows the T cells to directly recognize a specific antigen expressed on the tumor. In this chapter, we will review preclinical and clinical data for the different approaches.

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Abbreviations

A:

Adenine

APC:

Antigen-presenting cell

CAR:

Chimeric antigen receptor

CTL:

Cytotoxic T lymphocyte

CTLA-4:

Cytotoxic T lymphocyte antigen 4

DC:

Dendritic cell

DNA:

Deoxyribonucleic acid

EGFR:

Endothelial growth factor receptor

ELISA:

Enzyme-linked immunosorbent assay

GC:

Guanine and cytosine

GITR:

Glucocorticoid-induced tumor necrosis factor receptor

HLA:

Human leukocyte antigen

HMGB1:

High-mobility group box 1

IDH1:

Isocitrate dehydrogenase 1

IFN:

Interferon

Ig:

Immunoglobulin

LLC:

Lewis lung cancer

MAGEC1:

Melanoma antigen family C1

MAGEC2:

Melanoma antigen family C2

MHC:

Major histocompatibility complex

mRNA:

Messenger ribonucleic acid

MUC1:

Mucin 1

NK:

Natural killer

NSCLC:

Non-small-cell lung cancer

NY-ESO-1:

New York esophageal squamous cell carcinoma-1

ORF:

Open reading frame

OVA:

Ovalbumin

PAP:

Prostatic acid phosphatase

PD1:

Programmed cell death 1

PDL1:

Programmed cell death 1 ligand 1

PDL2:

Programmed cell death 1 ligand 2

PFS:

Progression-free survival

PSA:

Prostate-specific antigen

PSCA:

Prostate stem cell antigen

PSMA:

Prostate-specific membrane antigen

RNA:

Ribonucleic acid

RT-PCR:

Reverse transcriptase polymerase chain reaction

STEAP1:

Six-transmembrane epithelial antigen of the prostate 1

TAA:

Tumor-associated antigen

TERT:

Telomerase reverse transcriptase

Th:

T helper

TLR:

Toll-like receptor

Tmeso:

CAR T cells specifically targeting mesothelin

TPBG:

Trophoblast glycoprotein

UTR:

Untranslated region

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Acknowledgments

We would like to thank Henoch Hong, Ulrike Gnad-Vogt, Ulrich Kruse, and Mariola Fotin-Mleczek for discussions and suggestions.

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  1. CureVac AG, Paul-Ehrlich-Str. 15, 72076, Tübingen, Germany

    Katja Fiedler, Sandra Lazzaro, Johannes Lutz, Susanne Rauch & Regina Heidenreich

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  1. Katja Fiedler
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  2. Sandra Lazzaro
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  3. Johannes Lutz
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  4. Susanne Rauch
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Correspondence to Katja Fiedler .

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  1. Department of Translational Oncology, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Berlin, Germany

    Wolfgang Walther

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Fiedler, K., Lazzaro, S., Lutz, J., Rauch, S., Heidenreich, R. (2016). mRNA Cancer Vaccines. In: Walther, W. (eds) Current Strategies in Cancer Gene Therapy. Recent Results in Cancer Research, vol 209. Springer, Cham. https://doi.org/10.1007/978-3-319-42934-2_5

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