Abstract
DNA vaccines assisted by electroporation efficiently trigger antitumor cytotoxic CD8+ T cell responses in preclinical cancer models and hold potential for human use. They can be easily engineered to express either tumor-associated self-antigens, which are broadly expressed among tumor patients but also in healthy tissue, or tumor-specific neoantigens, which are uniquely expressed in tumors and differ among patients. Recently, it has been demonstrated that DNA vaccination generates both circulating and tissue-resident compartments of CD8+ T cells, which act concertedly against tumors. Here we describe the steps to obtain and test DNA vaccines against models of self-antigens and neoantigens in mice. It includes the evaluation of effector and memory CD8+ T cell responses, as well as assessing the antitumor potential in vivo using transplantable syngeneic tumor models.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ligtenberg M, Rojas-Colonelli N, Kiessling R et al (2013) NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses. Hum Vaccin Immunother 9:2189–2195
Ishikawa H, Ma Z, Barger G (2009) STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461:788–792
Roberts E, Broz M, Binnewies M et al (2016) Critical role for CD103+ /CD141+ dendritic cells bearing CCR7 for tumor antigen trafficking and priming of T cell immunity in melanoma. Cancer Cell 30:324–336
Tondini E, Arakelian T, Oosterhuis K et al (2019) A poly-neoantigen DNA vaccine synergizes with PD-1 blockade to induce T cell-mediated tumor control. Onco Targets Ther 8:1652539
Enamorado M, Iborra S, Priego E et al (2017) Enhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8+ T cells. Nat Commun 8:16073
Gálvez-Cancino F, López E, Menares E et al (2018) Vaccination-induced skin-resident memory CD8+T cells mediate strong protection against cutaneous melanoma. Onco Targets Ther 7:e1442163
Vrisekoop N, Monteiro J, Mandl J et al (2014) Revisiting thymic positive selection and the mature T cell repertoire for antigen. Immunity 41:181–190
Schwartzentruber D, Lawson D, Richards J et al (2011) gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med 364:2119–2127
Burrack A, Spartz E, Raynor J et al (2019) Combination PD-1 and PD-L1 blockade promotes durable neoantigen-specific T cell-mediated immunity in pancreatic ductal adenocarcinoma. Cell Rep 28:2140–2155.e6
Yost K, Satpathy A, Wells D et al (2019) Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat Med 25:1251–1259
Fritsch E, Rajasagi M, Ott P et al (2014) HLA-binding properties of tumor neoepitopes in humans. Cancer Immunol Res 2:522–529
Sahin U, Derhovanessian E, Miller M et al (2017) Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547:222–226
Aurisicchio L, Pallocca M, Ciliberto G et al (2018) The perfect personalized cancer therapy: cancer vaccines against neoantigens. J Exp Clin Cancer Res 37:86
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Cáceres-Morgado, P., Lladser, A. (2021). Tumor-Specific CD8+ T-Cell Responses Induced by DNA Vaccination. In: Sousa, Â. (eds) DNA Vaccines. Methods in Molecular Biology, vol 2197. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0872-2_12
Download citation
DOI: https://doi.org/10.1007/978-1-0716-0872-2_12
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-0871-5
Online ISBN: 978-1-0716-0872-2
eBook Packages: Springer Protocols