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.
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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
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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
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DOI: https://doi.org/10.1007/978-1-0716-0872-2_12
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Publisher Name: Humana, New York, NY
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