Wolchok, J. D. et al. Ultimate, 10-year outcomes with nivolumab plus ipilimumab in superior melanoma. N. Engl. J. Med. 392, 11–22 (2025).
Irvine, D. J., Maus, M. V., Mooney, D. J. & Wong, W. W. The way forward for engineered immune cell therapies. Science 378, 853–858 (2022).
Sharma, P. et al. Immune checkpoint remedy—present views and future instructions. Cell 186, 1652–1669 (2023).
Gaynor, N., Crown, J. & Collins, D. M. Immune checkpoint inhibitors: key trials and an rising position in breast most cancers. Semin. Most cancers Biol. 79, 44–57 (2022).
Patel, S. A. & Minn, A. J. Mixture most cancers remedy with immune checkpoint blockade: mechanisms and techniques. Immunity 48, 417–433 (2018).
Sellars, M. C., Wu, C. J. & Fritsch, E. F. Most cancers vaccines: constructing a bridge over troubled waters. Cell 185, 2770–2788 (2022).
Zappasodi, R., Merghoub, T. & Wolchok, J. D. Rising ideas for immune checkpoint blockade-based mixture therapies. Most cancers Cell 33, 581–598 (2018).
Ninmer, E. Ok., Xu, F. & Slingluff, C. L. Jr The landmark sequence: most cancers vaccines for strong tumors. Ann. Surg. Oncol. 32, 1443–1452 (2025).
Lin, M. J. et al. Most cancers vaccines: the subsequent immunotherapy frontier. Nat. Most cancers 3, 911–926 (2022).
Katsikis, P. D., Ishii, Ok. J. & Schliehe, C. Challenges in growing personalised neoantigen most cancers vaccines. Nat. Rev. Immunol. 24, 213–227 (2024).
Graciotti, M. & Kandalaft, L. E. Vaccines for most cancers prevention: exploring alternatives and navigating challenges. Nat. Rev. Drug Discov. https://doi.org/10.1038/s41573-024-01081-5 (2024).
Gilboa, E. The makings of a tumor rejection antigen. Immunity 11, 263–270 (1999).
Clark, Ok. T. & Trimble, C. L. Present standing of therapeutic HPV vaccines. Gynecol. Oncol. 156, 503–510 (2020).
De Plaen, E. et al. Immunogenic (tum−) variants of mouse tumor P815: cloning of the gene of tum− antigen P91A and identification of the tum− mutation. Proc. Natl Acad. Sci. USA 85, 2274–2278 (1988).
Matsushita, H. et al. Most cancers exome evaluation reveals a T-cell-dependent mechanism of most cancers immunoediting. Nature 482, 400–404 (2012).
Citadel, J. C. et al. Exploiting the mutanome for tumor vaccination. Most cancers Res. 72, 1081–1091 (2012).
Kvistborg, P. et al. Anti-CTLA-4 remedy broadens the melanoma-reactive CD8+ T cell response. Sci. Transl. Med. 6, 254ra128 (2014).
Subudhi, S. Ok. et al. Neoantigen responses, immune correlates, and favorable outcomes after ipilimumab therapy of sufferers with prostate most cancers. Sci. Transl. Med. 12, eaaz3577 (2020).
McGranahan, N. et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351, 1463–1469 (2016).
Aggarwal, C. et al. Evaluation of tumor mutational burden and outcomes in sufferers with numerous superior cancers handled with immunotherapy. JAMA Netw. Open 6, e2311181 (2023).
Turajlic, S. et al. Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer evaluation. Lancet Oncol. 18, 1009–1021 (2017).
Chen, X. et al. Mutant p53 in most cancers: from molecular mechanism to therapeutic modulation. Cell Dying Dis. 13, 974 (2022).
Karakas, B., Bachman, Ok. E. & Park, B. H. Mutation of the PIK3CA oncogene in human cancers. Br. J. Most cancers 94, 455–459 (2006).
Hofmann, M. H., Gerlach, D., Misale, S., Petronczki, M. & Kraut, N. Increasing the attain of precision oncology by drugging all KRAS mutants. Most cancers Discov. 12, 924–937 (2022).
Bonaventura, P. et al. Identification of shared tumor epitopes from endogenous retroviruses inducing high-avidity cytotoxic T cells for most cancers immunotherapy. Sci. Adv. 8, eabj3671 (2022).
Ott, P. A. et al. An immunogenic private neoantigen vaccine for sufferers with melanoma. Nature 547, 217–221 (2017).
Keskin, D. B. et al. Neoantigen vaccine generates intratumoral T cell responses in part Ib glioblastoma trial. Nature 565, 234–239 (2019).
Hilf, N. et al. Actively personalised vaccination trial for newly recognized glioblastoma. Nature 565, 240–245 (2019).
Johanns, T. M. et al. Detection of neoantigen-specific T cells following a customized vaccine in a affected person with glioblastoma. Oncoimmunology 8, e1561106 (2019).
Braun, D. A. et al. A neoantigen vaccine generates antitumour immunity in renal cell carcinoma. Nature 639, 474–482 (2025). This part I medical trial evaluated personalised peptide vaccines concentrating on neoantigens in sufferers with renal cell carcinoma following profitable surgical resection, with no relapse detected in 9 out of 9 vaccinated sufferers after 40 months of follow-up.
Saxena, M. et al. Atezolizumab plus personalised neoantigen vaccination in urothelial most cancers: a part 1 trial. Nat. Most cancers 6, 988–999 (2025).
Carreno, B. M. et al. A dendritic cell vaccine will increase the breadth and variety of melanoma neoantigen-specific T cells. Science 348, 803–808 (2015).
Everson, R. G. et al. TLR agonists polarize interferon responses along side dendritic cell vaccination in malignant glioma: a randomized part II trial. Nat. Commun. 15, 3882 (2024).
Fan, T. et al. Therapeutic most cancers vaccines: developments, challenges and prospects. Sign Transduct. Goal. Ther. 8, 450 (2023).
Rappaport, A. R. et al. A shared neoantigen vaccine mixed with immune checkpoint blockade for superior metastatic strong tumors: part 1 trial interim outcomes. Nat. Med. 30, 1013–1022 (2024).
Palmer, C. D. et al. Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for superior metastatic strong tumors: part 1 trial interim outcomes. Nat. Med. 28, 1619–1629 (2022).
D’Alise, A. M. et al. Part I trial of viral vector-based personalised vaccination elicits sturdy neoantigen-specific antitumor T-cell responses. Clin. Most cancers Res. 30, 2412–2423 (2024).
Yarchoan, M. et al. Personalised neoantigen vaccine and pembrolizumab in superior hepatocellular carcinoma: a part 1/2 trial. Nat. Med. 30, 1044–1053 (2024).
Zhang, X. et al. Neoantigen DNA vaccines are secure, possible, and induce neoantigen-specific immune responses in triple-negative breast most cancers sufferers. Genome Med. 16, 131 (2024).
Chaudhary, N., Weissman, D. & Whitehead, Ok. A. mRNA vaccines for infectious illnesses: ideas, supply and medical translation. Nat. Rev. Drug Discov. 20, 817–838 (2021).
O’Shea, A. E. et al. Part II trial of nelipepimut-S peptide vaccine in girls with ductal carcinoma in situ. Most cancers Prev. Res. (Phila.) 16, 331–341 (2023).
Mittendorf, E. A. et al. Efficacy and security evaluation of nelipepimut-S vaccine to stop breast most cancers recurrence: a randomized, multicenter, part III medical trial. Clin. Most cancers Res. 25, 4248–4254 (2019).
Montauti, E., Oh, D. Y. & Fong, L. CD4+ T cells in antitumor immunity. Traits Most cancers 10, 969–985 (2024).
Bijker, M. S. et al. Superior induction of anti-tumor CTL immunity by prolonged peptide vaccines includes extended, DC-focused antigen presentation. Eur. J. Immunol. 38, 1033–1042 (2008).
Rosalia, R. A. et al. Dendritic cells course of artificial lengthy peptides higher than entire protein, bettering antigen presentation and T‐cell activation. Eur. J. Immunol. 43, 2554–2565 (2013).
Kuna, M., Mahdi, F., Chade, A. R. & Bidwell, G. L. Molecular measurement modulates pharmacokinetics, biodistribution, and renal deposition of the drug supply biopolymer elastin-like polypeptide. Sci. Rep. 8, 7923 (2018).
Trevaskis, N. L., Kaminskas, L. M. & Porter, C. J. H. From sewer to saviour — concentrating on the lymphatic system to advertise drug publicity and exercise. Nat. Rev. Drug Discov. 14, 781–803 (2015).
Moynihan, Ok. D. et al. Enhancement of peptide vaccine immunogenicity by growing lymphatic drainage and boosting serum stability. Most cancers Immunol. Res. 6, 1025–1038 (2018).
Böttger, R., Hoffmann, R. & Knappe, D. Differential stability of therapeutic peptides with completely different proteolytic cleavage websites in blood, plasma and serum. PLoS ONE 12, e0178943 (2017).
Yu, X. et al. Melittin-lipid nanoparticles goal to lymph nodes and elicit a systemic anti-tumor immune response. Nat. Commun. 11, 1110 (2020).
Najafabadi, A. H. et al. Vaccine nanodiscs plus polyICLC elicit sturdy CD8+ T cell responses in mice and non-human primates. J. Management. Launch 337, 168–178 (2021).
Lynn, G. M. et al. Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly improve CD8 T-cell immunity to tumor antigens. Nat. Biotechnol. 38, 320–332 (2020).
Lynn, G. M. et al. In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that improve vaccine immunogenicity. Nat. Biotechnol. 33, 1201–1210 (2015).
Reddy, S. T. et al. Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nat. Biotechnol. 25, 1159–1164 (2007).
Teplensky, M. H. et al. Multi-antigen spherical nucleic acid most cancers vaccines. Nat. Biomed. Eng. 7, 911–927 (2023).
Bachmann, M. F. & Jennings, G. T. Vaccine supply: a matter of measurement, geometry, kinetics and molecular patterns. Nat. Rev. Immunol. 10, 787–796 (2010).
Baharom, F. et al. Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells. Nat. Immunol. 22, 41–52 (2021).
Kuai, R., Ochyl, L. J., Bahjat, Ok. S., Schwendeman, A. & Moon, J. J. Designer vaccine nanodiscs for personalised most cancers immunotherapy. Nat. Mater. 16, 489–496 (2016). This examine reported the event of artificial lipid nanodiscs carrying neoantigen peptides and adjuvant molecules that confirmed environment friendly concentrating on to lymph nodes, resulting in sturdy antitumour immunity in preclinical mouse fashions of most cancers.
Irvine, D. J., Aung, A. & Silva, M. Controlling timing and site in vaccines. Adv. Drug Deliv. Rev. 158, 91–115 (2020).
Baharom, F. et al. Systemic vaccination induces CD8+ T cells and remodels the tumor microenvironment. Cell 185, 4317–4332.e15 (2022). This examine demonstrated that nanoparticles carrying peptide antigens and molecular adjuvants administered intravenously can concurrently goal dendritic cells in lymphoid organs and immediately accumulate in tumour tissues, triggering simultaneous priming of recent T cell responses and remodelling the tumour microenvironment to advertise antitumour immunity.
Liu, H. et al. Construction-based programming of lymph-node concentrating on in molecular vaccines. Nature 507, 519–522 (2014). This examine demonstrated the idea of ‘albumin hitchhiking’ for the concentrating on of peptide antigens and molecular adjuvants to lymph nodes, exhibiting this to be a really potent technique for amplifying vaccine responses in preclinical mouse fashions of most cancers.
Ma, L. et al. Enhanced CAR–T cell exercise towards strong tumors by vaccine boosting via the chimeric receptor. Science 365, 162–168 (2019).
Rakhra, Ok. et al. Exploiting albumin as a mucosal vaccine chaperone for sturdy technology of lung-resident reminiscence T cells. Sci. Immunol. 6, eabd8003 (2021).
Wang, C. et al. Reprogramming NK cells and macrophages through mixed antibody and cytokine remedy primes tumors for elimination by checkpoint blockade. Cell Rep. 37, 110021 (2021).
Moynihan, Ok. D. et al. Eradication of huge established tumors in mice by mixture immunotherapy that engages innate and adaptive immune responses. Nat. Med. 22, 1402–1410 (2016).
Pant, S. et al. Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal most cancers: the part 1 AMPLIFY-201 trial. Nat. Med. 30, 531–542 (2024). This part I examine reported promising immunogenicity, relapse-free survival and general survival for pancreatic most cancers sufferers who have been optimistic for circulating tumour biomarkers following surgical resection and acquired a lymph node-targeted peptide vaccine concentrating on mutant KRAS antigen.
Devoe, C. E. et al. AMPLIFY-7P, a first-in-human security and efficacy trial of adjuvant mKRAS-specific lymph node focused amphiphile ELI-002 7P vaccine in sufferers with minimal residual illness–optimistic pancreatic and colorectal most cancers. J. Clin. Oncol. 42, 2636–2636 (2024).
Wainberg, Z. A. et al. Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal most cancers: part 1 AMPLIFY-201 trial closing outcomes. Nat. Med. https://doi.org/10.1038/s41591-025-03876-4 (2025).
McNeil, L.Ok. et al. 1473 AMPLIFY-7P part 1a: lymph node-targeted amphiphile therapeutic most cancers vaccine in sufferers with excessive relapse threat KRAS mutated pancreatic ductal adenocarcinoma and colorectal most cancers. J. Immunother. Most cancers https://doi.org/10.1136/jitc-2024-SITC2024.1473 (2024).
Elicio Therapeutics. A examine of ELI-002 7P in topics with KRAS/NRAS mutated strong tumors (AMPLIFY-7P). ClinicalTrials.gov https://www.clinicaltrials.gov/examine/NCT05726864 (2025).
Kranz, L. M. et al. Systemic RNA supply to dendritic cells exploits antiviral defence for most cancers immunotherapy. Nature 534, 396–401 (2016). This examine demonstrated that mRNA carried in near-neutral-charge LPXs administered intravenously can successfully goal, transfect and activate dendritic cells systemically, offering sturdy vaccine priming in preclinical mouse fashions, and reported early part I vaccination knowledge in most cancers sufferers.
Sahin, U. et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature 585, 107–112 (2020).
Karikó, Ok., Buckstein, M., Ni, H. & Weissman, D. Suppression of RNA recognition by Toll-like receptors: the affect of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005).
Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA supply. Nat. Rev. Mater. 6, 1078–1094 (2021).
Akinc, A. et al. The Onpattro story and the medical translation of nanomedicines containing nucleic acid-based medication. Nat. Nanotechnol. 14, 1084–1087 (2019).
Lee, J. M. et al. The part 3 INTerpath-002 examine design: individualized neoantigen remedy (INT) V940 (mRNA-4157) plus pembrolizumab vs placebo plus pembrolizumab for resected early-stage non-small-cell lung most cancers (NSCLC). J. Clin. Oncol. 42, TPS8116 (2024).
Alameh, M.-G. et al. Lipid nanoparticles improve the efficacy of mRNA and protein subunit vaccines by inducing sturdy T follicular helper cell and humoral responses. Immunity 54, 2877–2892.e7 (2021). This examine was one of many first to display that LNP formulations used for mRNA supply have intrinsic adjuvant exercise that promotes immunity to co-administered antigens.
Verbeke, R., Hogan, M. J., Loré, Ok. & Pardi, N. Innate immune mechanisms of mRNA vaccines. Immunity 55, 1993–2005 (2022).
Semple, S. C. et al. Rational design of cationic lipids for siRNA supply. Nat. Biotechnol. 28, 172–176 (2010).
Kowalski, P. S., Rudra, A., Miao, L. & Anderson, D. G. Delivering the messenger: advances in applied sciences for therapeutic mRNA supply. Mol. Ther. 27, 710–728 (2019).
Hajj, Ok. A. & Whitehead, Ok. A. Instruments for translation: non-viral supplies for therapeutic mRNA supply. Nat. Rev. Mater. 2, 17056 (2017).
Carvalho, T. Personalised anti-cancer vaccine combining mRNA and immunotherapy examined in melanoma trial. Nat. Med. 29, 2379–2380 (2023).
Weber, J. S. et al. Individualised neoantigen remedy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, part 2b examine. Lancet 403, 632–644 (2024). This randomized part II medical trial reported a considerably diminished threat of dying as a consequence of recurrence in melanoma sufferers who acquired a customized mRNA neoantigen-targeting vaccine together with checkpoint blockade versus checkpoint blockade alone.
Ladwa, R. et al. 940TiP INTerpath-007: a part II/III, adaptive, randomized examine of neoadjuvant and adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) for therapy of resectable regionally superior (LA) cutaneous squamous cell carcinoma (cSCC). Ann. Oncol. 35, S652–S653 (2024).
Motzer, R. J. et al. INTerpath-004: a part 2, randomized, double-blind examine of adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) or placebo for renal cell carcinoma (RCC). J. Clin. Oncol. 43, TPS610 (2025).
Sonpavde, G. P. et al. Part 1/2 INTerpath-005 examine: V940 (mRNA-4157) plus pembrolizumab with or with out enfortumab vedotin (EV) for resected high-risk muscle-invasive urothelial carcinoma (MIUC). J. Clin. Oncol. 43, TPS893 (2025).
Lindsay, Ok. E. et al. Visualization of early occasions in mRNA vaccine supply in non-human primates through PET–CT and near-infrared imaging. Nat. Biomed. Eng. 3, 371–380 (2019).
Liang, F. et al. Environment friendly concentrating on and activation of antigen-presenting cells in vivo after modified mRNA vaccine administration in rhesus macaques. Mol. Ther. 25, 2635–2647 (2017).
Buckley, M. et al. Visualizing lipid nanoparticle trafficking for mRNA vaccine supply in non-human primates. Mol. Ther. 33, 1105–1117 (2025).
Blizard, G. S. et al. Monitoring mRNA vaccine antigen expression in vivo utilizing PET/CT. Nat. Commun. 16, 2234 (2025).
Gainor, J. F. et al. T-cell responses to individualized neoantigen remedy mRNA-4157 (V940) alone or together with pembrolizumab within the part 1 KEYNOTE-603 examine. Most cancers Discov. 14, 2209–2223 (2024).
Low, J. G. et al. A part I/II randomized, double-blinded, placebo-controlled trial of a self-amplifying Covid-19 mRNA vaccine. npj Vaccines 7, 161 (2022).
Saraf, A. et al. An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a part 2/3 randomized trial. Nat. Med. 30, 1363–1372 (2024).
Zhang, Y. et al. Small round RNAs as vaccines for most cancers immunotherapy. Nat. Biomed. Eng. 9, 249–267 (2025).
Gong, Z. et al. Current advances and views on the event of round RNA most cancers vaccines. npj Vaccines 10, 41 (2025).
First self-amplifying mRNA vaccine authorised. Nat. Biotechnol. 42, 4 (2024).
Yu, J. et al. Focused LNPs ship IL-15 superagonists mRNA for precision most cancers remedy. Biomaterials 317, 123047 (2025).
Zhang, D. et al. Enhancing CRISPR/Cas gene enhancing via modulating mobile mechanical properties for most cancers remedy. Nat. Nanotechnol. 17, 777–787 (2022).
Hu, X. et al. The hybrid lipoplex induces cytoskeletal rearrangement through autophagy/RhoA signaling pathway for enhanced anticancer gene remedy. Nat. Commun. 16, 339 (2025).
Grunwitz, C. et al. HPV16 RNA-LPX vaccine mediates full regression of aggressively rising HPV-positive mouse tumors and establishes protecting T cell reminiscence. Oncoimmunology 8, e1629259 (2019).
Salomon, N. et al. Native radiotherapy and E7 RNA-LPX vaccination present enhanced therapeutic efficacy in preclinical fashions of HPV16+ most cancers. Most cancers Immunol. Immunother. 71, 1975–1988 (2022).
Lopez, J. et al. Autogene cevumeran with or with out atezolizumab in superior strong tumors: a part 1 trial. Nat. Med. 31, 152–164 (2025).
Rojas, L. A. et al. Personalised RNA neoantigen vaccines stimulate T cells in pancreatic most cancers. Nature 618, 144–150 (2023). This paper reported outcomes from a small part I medical trial exhibiting that mRNA vaccines concentrating on personalised neoantigens have been immunogenic and elicited encouraging recurrence-free and general survival in pancreatic most cancers sufferers at excessive threat for relapse following surgical procedure.
Sethna, Z. et al. RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic most cancers. Nature 639, 1042–1051 (2025).
Mendez-Gomez, H. R. et al. RNA aggregates harness the hazard response for potent most cancers immunotherapy. Cell 187, 2521–2535.e21 (2024).
Haabeth, O. A. W. et al. mRNA vaccination with charge-altering releasable transporters elicits human T cell responses and cures established tumors in mice. Proc. Natl Acad. Sci. USA 115, E9153–E9161 (2018).
Ben-Akiva, E., Chapman, A., Mao, T. & Irvine, D. J. Linking vaccine adjuvant mechanisms of motion to operate. Sci. Immunol. 10, eado5937 (2025).
Pulendran, B., Arunachalam, P. S. & O’Hagan, D. T. Rising ideas within the science of vaccine adjuvants. Nat. Rev. Drug Discov. https://doi.org/10.1038/s41573-021-00163-y (2021).
Zimmermann, J. et al. A novel prophylaxis technique utilizing liposomal vaccine adjuvant CAF09b protects towards influenza virus illness. Int. J. Mol. Sci. 23, 1850 (2022).
Mørk, S. Ok. et al. First in man examine: Bcl-Xl_42-CAF®09b vaccines in sufferers with regionally superior prostate most cancers. Entrance. Immunol. 14, 1122977 (2023).
Mørk, S. Ok. et al. Dose escalation examine of a customized peptide-based neoantigen vaccine (EVX-01) in sufferers with metastatic melanoma. J. Immunother. Most cancers 12, e008817 (2024).
Banga, R. J., Chernyak, N., Narayan, S. P., Nguyen, S. T. & Mirkin, C. A. Liposomal spherical nucleic acids. J. Am. Chem. Soc. 136, 9866–9869 (2014).
Ferrer, J. R. et al. Construction-dependent biodistribution of liposomal spherical nucleic acids. ACS Nano 14, 1682–1693 (2020).
Meckes, B., Banga, R. J., Nguyen, S. T. & Mirkin, C. A. Enhancing the steadiness and immunomodulatory exercise of liposomal spherical nucleic acids via lipid‐tail DNA modifications. Small 14, 1702909 (2018).
Daniel, W. L., Lorch, U., Combine, S. & Bexon, A. S. A primary-in-human part 1 examine of cavrotolimod, a TLR9 agonist spherical nucleic acid, in wholesome contributors: proof of immune activation. Entrance. Immunol. 13, 1073777 (2022).
Seenappa, L. M. et al. Amphiphile-CpG vaccination induces potent lymph node activation and COVID-19 immunity in mice and non-human primates. npj Vaccines 7, 128 (2022).
Martin, J. T. et al. Mixed PET and whole-tissue imaging of lymphatic-targeting vaccines in non-human primates. Biomaterials 275, 120868 (2021).
Speetjens, F. M. et al. Intradermal vaccination of HPV-16 E6 artificial peptides conjugated to an optimized Toll-like receptor 2 ligand exhibits security and potent T cell immunogenicity in sufferers with HPV-16 optimistic (pre-)malignant lesions. J. Immunother. Most cancers 10, e005016 (2022).
Zhivaki, D. et al. Inflammasomes inside hyperactive murine dendritic cells stimulate long-lived T cell-mediated anti-tumor immunity. Cell Rep. 33, 108381 (2020).
Zanoni, I., Tan, Y., Di Gioia, M., Springstead, J. R. & Kagan, J. C. By capturing inflammatory lipids launched from dying cells, the receptor CD14 induces inflammasome-dependent phagocyte hyperactivation. Immunity 47, 697–709.e3 (2017).
Silva, M. et al. A particulate saponin/TLR agonist vaccine adjuvant alters lymph move and modulates adaptive immunity. Sci. Immunol. 6, eabf1152 (2021).
Bengtsson, Ok. L., Morein, B. & Osterhaus, A. D. ISCOM technology-based Matrix M™ adjuvant: success in future vaccines depends on formulation. Skilled Rev. Vaccines 10, 401–403 (2011).
Mochida, Y. & Uchida, S. mRNA vaccine designs for optimum adjuvanticity and supply. RNA Biol. 21, 422–448 (2024).
Yang, Ok. et al. Biodegradable lipid-modified poly(guanidine thioctic acid)s: a fortifier of lipid nanoparticles to advertise the efficacy and security of mRNA most cancers vaccines. J. Am. Chem. Soc. 146, 11679–11693 (2024).
Omo-Lamai, S. et al. Limiting endosomal harm sensing reduces irritation triggered by lipid nanoparticle endosomal escape. Nat. Nanotechnol. 20, 1285–1297 (2025).
Chaudhary, N. et al. Amine headgroups in ionizable lipids drive immune responses to lipid nanoparticles by binding to the receptors TLR4 and CD1d. Nat. Biomed. Eng. 8, 1483–1498 (2024).
Barbier, A. J., Jiang, A. Y., Zhang, P., Wooster, R. & Anderson, D. G. The medical progress of mRNA vaccines and immunotherapies. Nat. Biotechnol. 40, 840–854 (2022).
Han, X. et al. Adjuvant lipidoid-substituted lipid nanoparticles increase the immunogenicity of SARS-CoV-2 mRNA vaccines. Nat. Nanotechnol. https://doi.org/10.1038/s41565-023-01404-4 (2023).
Zhang, Y. et al. STING agonist-derived LNP-mRNA vaccine enhances protecting immunity towards SARS-CoV-2. Nano Lett. 23, 2593–2600 (2023).
Miao, L. et al. Supply of mRNA vaccines with heterocyclic lipids will increase anti-tumor efficacy by STING-mediated immune cell activation. Nat. Biotechnol. 37, 1174–1185 (2019).
Chen, W., Yan, W. & Huang, L. A easy however efficient most cancers vaccine consisting of an antigen and a cationic lipid. Most cancers Immunol. Immunother. 57, 517–530 (2008).
Gandhapudi, S. Ok. et al. Antigen priming with enantiospecific cationic lipid nanoparticles induces potent antitumor CTL responses via novel induction of a sort I IFN response. J. Immunol. 202, 3524–3536 (2019).
Rumfield, C. S., Pellom, S. T., Morillon, Y. M. II, Schlom, J. & Jochems, C. Immunomodulation to boost the efficacy of an HPV therapeutic vaccine. J. Immunother. Most cancers 8, e000612 (2020).
Kahles, A. et al. Complete evaluation of other splicing throughout tumors from 8,705 sufferers. Most cancers Cell 34, 211–224.e6 (2018).
Reynisson, B., Alvarez, B., Paul, S., Peters, B. & Nielsen, M. NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand knowledge. Nucleic Acids Res. 48, W449–W454 (2020).
Li, G., Iyer, B., Prasath, V. B. S., Ni, Y. & Salomonis, N. DeepImmuno: deep learning-empowered prediction and technology of immunogenic peptides for T-cell immunity. Temporary. Bioinform. 22, bbab160 (2021).
Schmidt, J. et al. Prediction of neo-epitope immunogenicity reveals TCR recognition determinants and supplies perception into immunoediting. Cell Rep. Med. 2, 100194 (2021).
Wu, J. et al. DeepHLApan: a deep studying method for neoantigen prediction contemplating each HLA-peptide binding and immunogenicity. Entrance. Immunol. 10, 2559 (2019).
Kreiter, S. et al. Mutant MHC class II epitopes drive therapeutic immune responses to most cancers. Nature 520, 692–696 (2015).
Martin, S. D. et al. Low mutation burden in ovarian most cancers could restrict the utility of neoantigen-targeted vaccines. PloS ONE 11, e0155189 (2016).
Sahin, U. et al. Personalised RNA mutanome vaccines mobilize poly-specific therapeutic immunity towards most cancers. Nature 547, 222–226 (2017).
Chen, H. et al. Chemical and topological design of multicapped mRNA and capped round RNA to enhance translation. Nat. Biotechnol. https://doi.org/10.1038/s41587-024-02393-y (2025).
Chen, R. et al. Engineering round RNA for enhanced protein manufacturing. Nat. Biotechnol. 41, 262–272 (2023).
Wesselhoeft, R. A., Kowalski, P. S. & Anderson, D. G. Engineering round RNA for potent and steady translation in eukaryotic cells. Nat. Commun. 9, 2629 (2018).
Feng, Z. et al. An in vitro-transcribed round RNA targets the mitochondrial interior membrane cardiolipin to ablate EIF4G2+/PTBP1+ pan-adenocarcinoma. Nat. Most cancers 5, 30–46 (2024).
Morse, M. A. et al. Medical trials of self-replicating RNA-based most cancers vaccines. Most cancers Gene Ther. 30, 803–811 (2023).
Aliahmad, P., Miyake-Stoner, S. J., Geall, A. J. & Wang, N. S. Subsequent technology self-replicating RNA vectors for vaccines and immunotherapies. Most cancers Gene Ther. 30, 785–793 (2023).
Kim, D. Y. et al. Enhancement of protein expression by alphavirus replicons by designing self-replicating subgenomic RNAs. Proc. Natl Acad. Sci. USA 111, 10708–10713 (2014).
Oda, Y. et al. 12-month persistence of immune responses to self-amplifying mRNA COVID-19 vaccines: ARCT-154 versus BNT162b2 vaccine. Lancet Infect. Dis. https://doi.org/10.1016/s1473-3099(24)00615-7 (2024).
