The DOI matches its Crossref record; 26 of the 28 references it cites were found in a registry or an index.
Direct Injection of Protamine-protected mRNA: Results of a Phase 1/2 Vaccination Trial in Metastatic Melanoma Patients
Abstract
In mice, injection of messenger RNA (mRNA) coding for tumor-associated antigens can induce antitumor immune responses and therefore offers a broadly applicable immunotherapy approach. We injected intradermally protamine-stabilized mRNAs coding for Melan-A, Tyrosinase, gp100, Mage-A1, Mage-A3, and Survivin in 21 metastatic melanoma patients. In 10 patients keyhole limpet hemocyanin (KLH) was added to the vaccine. Granulocyte macrophage colony-stimulating factor was applied as an adjuvant. Endpoints were toxicity and immune responses. No adverse events more than grade II have been observed. During treatment the frequency of Foxp3+/CD4+ regulatory T cells was significantly decreased upon mRNA vaccination in peripheral blood of the patients in the KLH arm, whereas myeloid suppressor cells (CD11b+HLA-DR lo monocytes) were reduced in the patients not receiving KLH. A reproducible increase of vaccine-directed T cells was observed in 2 of 4 immunologically evaluable patients. One of 7 patients with measurable disease showed a complete response. In conclusion, we show here that direct injection of protamine-protected mRNA is feasible and safe. The significant influence of the treatment on the frequency of immunosuppressive cells, the increase of vaccine-directed T cells upon treatment in a subset of patients together with the demonstration of a complete clinical response encourage further clinical investigation of the protamine-mRNA vaccine.
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“Various RNA vaccines have been evaluated in human clinical trials, including naked and formulated non-amplifying mRNA (37-39) and self-amplifying RNA packaged in VRPs (25).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [39]
In the citing paper
“Those studies showed RNA vaccines to be well tolerated and immunogenic.”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [39]
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Cites
Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., Evdemon-Hogan, M., Conejo-Garcia, J. R., Zhang, L., Burow, M., et al. (2004) · Nature Medicine · doi:10.1038/nm1093 · Cited by 5,151
Direct Gene Transfer into Mouse Muscle in Vivo
Wolff, J. A., Malone, R. W., Williams, P., Chong, W., Acsadi, G., Jani, A., & Felgner, P. L. (1990) · Science · doi:10.1126/science.1690918 · Cited by 4,173
CD4+CD25+ suppressor T cells: more questions than answers
Shevach, E. M. (2002) · Nature reviews. Immunology · doi:10.1038/nri821 · Cited by 2,097
Caligiuri, M. A. (2008) · Blood · doi:10.1182/blood-2007-09-077438 · Cited by 1,980
Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo.
Boczkowski, D., Nair, S. K., Snyder, D., & Gilboa, E. (1996) · The Journal of experimental medicine · doi:10.1084/jem.184.2.465 · Cited by 915
Increase of regulatory T cells in the peripheral blood of cancer patients.
Wolf, A. M., Wolf, D. G. F., Steurer, M., Gastl, G., Gunsilius, E., & Grubeck-Loebenstein, B. (2003) · PubMed · Cited by 655
Filipazzi, P., Valenti, R., Huber, V., Pilla, L., Canese, P., Iero, M., Castelli, C., Mariani, L., Parmiani, G., & Rivoltini, L. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.08.5829 · Cited by 646
(1995) · PubMed · Cited by 330
Results of the First Phase I/II Clinical Vaccination Trial With Direct Injection of mRNA
Weide, B., Carralot, J.-P., Reese, A., Scheel, B., Eigentler, T. K., Hoerr, I., Rammensee, H.-G., Garbe, C., & Pascolo, S. (2008) · Journal of Immunotherapy · doi:10.1097/cji.0b013e31815ce501 · Cited by 261 · cited 2×
“We established that this vaccination approach is feasible and safe, but clinical or immunologic responses were inconclusive.(7,8) After this first clinical trial, the mRNA concept was modified for the study presented here, as follows: (1) we used 6 defined mRNAs encoding known melanoma-associated antigens (Melan-A, Ty…”
BackgroundMethodSelf-citationSteitz, J., Brück, J., Lenz, J., Knop, J., & Tüting, T. (2001) · PubMed · Cited by 214
Cited by
Sorted by citations
Items 101–200 of 378
Sugar-Nanocapsules Imprinted with Microbial Molecular Patterns for mRNA Vaccination
Son, S., Nam, J., Zenkov, I., Ochyl, L. J., Xu, Y., Scheetz, L. M., Shi, J., Farokhzad, O. C., & Moon, J. J. (2020) · Nano Letters · doi:10.1021/acs.nanolett.9b03483 · Cited by 94
Personalized pancreatic cancer therapy: from the perspective of mRNA vaccine
Huang, X., Zhang, G., Tang, T., Gao, X., & Liang, T. (2022) · Military Medical Research · doi:10.1186/s40779-022-00416-w · Cited by 98
Use of Protamine in Nanopharmaceuticals—A Review
Ruseska, I., Fresacher, K., Petschacher, C., & Zimmer, A. (2021) · Nanomaterials · doi:10.3390/nano11061508 · Cited by 93
Selmi, A., Vascotto, F., Kautz‐Neu, K., Türeci, Ö., Şahin, U., von Stebut, E., Diken, M., & Kreiter, S. (2016) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-016-1869-7 · Cited by 90
Synthetic Messenger RNA-Based Vaccines: From Scorn to Hype
Pascolo, S. (2021) · Viruses · doi:10.3390/v13020270 · Cited by 87
“published in 2009 [13] and one in renal cell carcinoma patients published in 2010 [11].”
ResultSelf-citationDeliver the promise: RNAs as a new class of molecular entities for therapy and vaccination
Yu, A., & Tu, M. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107967 · Cited by 94
“Actually, before the COVID-19 pandemic, many mRNA vaccines against other infectious and malignant diseases had been investigated in the clinic (Bahl et al., 2017; Cafri et al., 2020; Leal et al., 2018; Papachristofilou et al., 2019; Rittig et al., 2011; Van Gulck et al., 2012; Weide et al., 2009), amid many challenges…”
BackgroundScreening of mRNA Chemical Modification to Maximize Protein Expression with Reduced Immunogenicity
Uchida, S., Kataoka, K., & Itaka, K. (2015) · Pharmaceutics · doi:10.3390/pharmaceutics7030137 · Cited by 90
“To date, this has limited the application of mRNA mainly to vaccine therapy [14–16].”
A new developing class of gene delivery: messenger RNA-based therapeutics
Zhao, M., Ahern, J. O., Lyu, J., Pierucci, L., Zhou, D., & Wang, W. (2017) · Biomaterials Science · doi:10.1039/c7bm00712d · Cited by 95
Lorenzi, J. C. C., Trombone, A. P. F., Rocha, C. D., de Almeida, L. P., Lousada, R. L., Malardo, T., Fontoura, I. C., Rossetti, R. A. M., Gembre, A. F., Silva, A. M., et al. (2010) · BMC Biotechnology · doi:10.1186/1472-6750-10-77 · Cited by 84
“Recently, Weid [4] concluded the second phase 1/2 vaccination trial in metastatic melanoma patients.”
BackgroundInfluentialClinical development and approval of COVID-19 vaccines
Kalinke, U., Barouch, D. H., Rizzi, R., Lagkadinou, E., Türeci, Ö., Pather, S., & Neels, P. (2022) · Expert Review of Vaccines · doi:10.1080/14760584.2022.2042257 · Cited by 86
Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles
Rodríguez‐Gascón, A., del Pozo‐Rodríguez, A., & Solinís, M. Á. (2014) · International Journal of Nanomedicine · doi:10.2147/ijn.s39810 · Cited by 79
“There are some experiences in Phase I/II clinical vaccination trials with mRNA that codes for tumor antigens; 29,30 these studies have shown that the treatment is feasible and safe, although the clinical effectiveness for antitumor immuno-therapy must be evaluated in further trials.”
FLT3 Ligand Enhances the Cancer Therapeutic Potency of Naked RNA Vaccines
Kreiter, S., Diken, M., Selmi, A., Diekmann, J., Attig, S., Hüsemann, Y., Koslowski, M., Huber, C., Türeci, Ö., & Sahin, U. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-0291 · Cited by 75
mRNA Cancer Vaccines: Construction and Boosting Strategies
Liu, X., Huang, P., Yang, R., & Deng, H. (2023) · ACS Nano · doi:10.1021/acsnano.3c05635 · Cited by 79
Electroporation-enhanced delivery of nucleic acid vaccines
Broderick, K. E., & Humeau, L. M. P. F. (2014) · Expert Review of Vaccines · doi:10.1586/14760584.2015.990890 · Cited by 74
Debus, H., Baumhof, P., Probst, J., & Kissel, T. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.09.007 · Cited by 74
“This approach is under investigation for several therapeutic applications, such as tumor vaccination [8], for example in metastatic melanoma [9].”
BackgroundmRNA vaccines: Past, present, future
Karam, M., & Daoud, G. (2022) · Asian Journal of Pharmaceutical Sciences · doi:10.1016/j.ajps.2022.05.003 · Cited by 76
“Metastatic melanoma Melan-A, Tyrosinase, gp100, Mage-A1, Mage-A3, Survivin N/A Phase I/II clinical trial (NCT00204607) - Activation of Th1 cells via TLR7/8 - Decrease of immunosuppressive cells - Increased vaccine-directed T cells [20]”
BackgroundThe mRNA Vaccine Revolution: COVID-19 Has Launched the Future of Vaccinology
Ye, Z., Harmon, J., Ni, W., Li, Y., Wich, D., & Xu, Q. (2023) · ACS Nano · doi:10.1021/acsnano.2c12584 · Cited by 72
mRNA – A game changer in regenerative medicine, cell-based therapy and reprogramming strategies
Chabanovska, O., Galow, A.-M., David, R., & Lemcke, H. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114002 · Cited by 81
“vaccine to medicate metastatic melanoma patients [26,27].”
Vallazza, B., Petri, S., Poleganov, M. A., Eberle, F., Kuhn, A. N., & Şahin, U. (2015) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1288 · Cited by 74
Dendrimer-Coated Gold Nanoparticles for Efficient Folate-Targeted mRNA Delivery In Vitro
Mbatha, L. S., Maiyo, F., Daniels, A. N., & Singh, M. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13060900 · Cited by 71
“The feasibility and non-toxicity of naked mRNA and mRNA complexed with protamine were demonstrated in human patients via intradermal injections, resulting in promising immunological responses [7,8].”
BackgroundStraight to the point: targeted mRNA-delivery to immune cells for improved vaccine design
Clemente, B., Denis, M., Silveira, C. P., Schiavetti, F., Brazzoli, M., & Stranges, D. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1294929 · Cited by 71
“To overcome the antivector immunity-dependent decrease of response related to viral vectors, alternative technologies have been used, such as RNA-peptide conjugates (187, 188), polymers (189) and lipid nanoparticles (7).”
MethodSelf-Replicating RNA Viruses for RNA Therapeutics
Lundstrom, K. H. (2018) · Molecules · doi:10.3390/molecules23123310 · Cited by 66
“cancer immunotherapy [4,5], vaccine development against infectious diseases [6,7], protein replacement [8], and gene editing [9].”
BackgroundLatest Development on RNA-Based Drugs and Vaccines
Lundstrom, K. H. (2018) · Future Science OA · doi:10.4155/fsoa-2017-0151 · Cited by 65
mRNA-Based Therapeutics in Cancer Treatment
Sun, H., Zhang, Y., Wang, G., Yang, W., & Xu, Y. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020622 · Cited by 65
The paradigm shift in treatment from Covid-19 to oncology with mRNA vaccines
Wei, J., & Hui, A.-M. (2022) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2022.102405 · Cited by 57
Lint, S. V., Heirman, C., Thielemans, K., & Breckpot, K. (2013) · Human Vaccines & Immunotherapeutics · doi:10.4161/hv.22661 · Cited by 59
RNA vaccines for cancer: Principles to practice
Guasp, P., Reiche, C., Sethna, Z. M., & Balachandran, V. P. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.05.005 · Cited by 64
Advances of mRNA vaccine in tumor: a maze of opportunities and challenges
Yuan, Y., Gao, F., Chang, Y., Zhao, Q., & He, X. (2023) · Biomarker Research · doi:10.1186/s40364-023-00449-w · Cited by 60
Tockary, T. A., Abbasi, S., Matsui-Masai, M., Hayashi, A., Yoshinaga, N., Boonstra, E., Wang, Z., Fukushima, S., Kataoka, K., & Uchida, S. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2214320120 · Cited by 56
“In parallel, vigorous efforts have been devoted to designing safe and effective immunostimulatory adjuvants for robust immunization in cancer vaccines over the past years (2, 6, 7).”
BackgroundNanotechnologies in Delivery of DNA and mRNA Vaccines to the Nasal and Pulmonary Mucosa
Tang, J., Cai, L., Xu, C., Sun, S., Liu, Y., Rosenecker, J., & Guan, S. (2022) · Nanomaterials · doi:10.3390/nano12020226 · Cited by 54
RNA therapeutics: Identification of novel targets leading to drug discovery
Qadir, M. I., Bukhat, S., Rasul, S., Manzoor, H., & Manzoor, M. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.29364 · Cited by 57
“Altogether, it also increases stability but with the disadvantage of reduced antigen expression.(57) Besides, combining IVT‐mRNA‐protamine complex and naked IVT‐mRNA results in enhanced translational effectiveness and immune‐stimulatory effect.”
Luo, F., Zheng, L., Hu, Y., Liu, S., Wang, Y., Xiong, Z., Hu, X., & Tan, F. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.00605 · Cited by 56
Vaccination with Messenger RNA: A Promising Alternative to DNA Vaccination
Tombácz, I., Weissman, D., & Pardi, N. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0872-2_2 · Cited by 55
Willis, E., Pardi, N., Parkhouse, K., Mui, B. L., Tam, Y. K., Weissman, D., & Hensley, S. E. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aav5701 · Cited by 54
Advances in mRNA therapeutics for cancer immunotherapy: From modification to delivery
Han, G., Noh, D., Lee, H., Lee, S., Kim, S., Yoon, H. Y., & Hyeon, L. S. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114973 · Cited by 53
“, have been designed for efficient in vitro and in vivo delivery, showing successful delivery and enhanced therapeutic efficacy [32-37].”
Design of in vitro Transcribed mRNA Vectors for Research and Therapy
Tusup, M., French, L. E., Matos, M. D., Gatfield, D., Kündig, T. M., & Pascolo, S. (2019) · CHIMIA International Journal for Chemistry · doi:10.2533/chimia.2019.391 · Cited by 55
Self-citationmRNA vaccines: a new era in vaccine development
Chandra, S., Wilson, J. C., Good, D. M., & Wei, M. Q. (2024) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.32604/or.2024.043987 · Cited by 58
“Another study involving patients with melanoma showed that mRNA encoding survivin and other melanoma-associated tumor antigens led to the creation of a greater number of antigen-speci fi c T-cells [89].”
BackgroundBacterial outer membrane vesicles as a candidate tumor vaccine platform
Wang, S., Guo, J., Bai, Y., Sun, C., Wu, Y., Liu, Z., Liu, X., Wang, Y., Wang, Z., Zhang, Y., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.987419 · Cited by 53
“At the same time, keyhole limpet hemocyanin (KLH) was added to the vaccine in 10 patients, the results showed that the frequency of Foxp3 +/CD4 + regulatory T cells was significantly decreased in patients treated with KLH, and the frequency of bone marrow suppressor cells (CD11b + HLA-DR LO monocytes) was decreased in…”
BackgroundZickler, A. M., Liang, X., Gupta, D., Mamand, D. R., Luca, M. D., Corso, G., Errichelli, L., Hean, J., Sen, T., Elsharkasy, O. M., et al. (2024) · Advanced Science · doi:10.1002/advs.202407619 · Cited by 55
Uchida, S., Yoshinaga, N., Yanagihara, K., Yuba, E., Kataoka, K., & Itaka, K. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.09.033 · Cited by 52
The Importance of RNA-Based Vaccines in the Fight against COVID-19: An Overview
Machado, B. A. S., Hodel, K. V. S., Fonseca, L. M. D. S., Mascarenhas, L. A. B., Andrade, L. P. C. D. S., Rocha, V. P. C., Soares, M. B. P., Berglund, P., Duthie, M. S., Reed, S. G., et al. (2021) · Vaccines · doi:10.3390/vaccines9111345 · Cited by 55
“Soon after, the same group published a phase I/II trial of a protamine-protected mRNA vaccine in metastatic melanoma patients (NCT00204607), demonstrating that protamine-protected mRNA was not only safe but generated more promising clinical efficacy [73].”
BackgroundmRNA vaccines in the prevention and treatment of diseases
Gu, Y., Duan, J., Yang, N., Yang, Y., & Zhao, X. (2022) · MedComm · doi:10.1002/mco2.167 · Cited by 54
mRNA vaccines and their delivery strategies: A journey from infectious diseases to cancer
Malla, R. R., Srilatha, M., Farran, B., & Nagaraju, G. P. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.10.024 · Cited by 51
Nanomaterials for direct and indirect immunomodulation: A review of applications
Kubackova, J., Zbytovská, J., & Holas, O. (2019) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2019.105139 · Cited by 48
Progress in Neoantigen Targeted Cancer Immunotherapies
Han, X., Ma, X., Li, Y., Wei, Y.-Q., Peng, Y., & Wei, X. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00728 · Cited by 49
Messenger RNA-Based Therapeutics and Vaccines: What’s beyond COVID-19?
Li, D., Liu, C., Li, Y., Tenchov, R., Sasso, J. M., Zhang, D., Li, D., Zou, L., Wang, X., & Zhou, Q. A. (2023) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.3c00047 · Cited by 50
Polyplex designs for improving the stability and safety of RNA therapeutics
Uchida, S., Lau, C. Y. J., Oba, M., & Miyata, K. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114972 · Cited by 46
Takanashi, A., Pouton, C. W., & Al-Wassiti, H. A. (2023) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.2c01024 · Cited by 48
State of the Art in Tumor Antigen and Biomarker Discovery
Even-Desrumeaux, K., Baty, D., & Chames, P. (2011) · Cancers · doi:10.3390/cancers3022554 · Cited by 46
“have been performed employing mRNA transfected DCs or injecting mRNA directly into patients with prostate cancer, renal cancer, ovarian cancer, lung cancer, breast cancer, pediatric brain cancer, neuroblastome, and melanoma [58-63].”
mRNA Cancer Vaccines—Messages that Prevail
Grunwitz, C. R., & Kranz, L. M. (2017) · Current topics in microbiology and immunology · doi:10.1007/82_2017_509 · Cited by 47
RNA Vaccines in Cancer Treatment
Bringmann, A., Held, S. A. E., Heine, A., & Brossart, P. (2010) · BioMed Research International · doi:10.1155/2010/623687 · Cited by 45
“21 Arm 1: 11 Arm 2: 10 Vaccine directed T cells: 2/4 Arm 1: 1/11 CR 4/11 NED Arm 2: 1/10 NED [99]”
Electrical Stimulation for Immune Modulation in Cancer Treatments
Das, R., Langou, S., Le, T. T., Prasad, P., Lin, F., & Nguyen, T. D. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.795300 · Cited by 44
“Lastly, genetic materials like DNA or RNA plasmids are also used as cancer vaccines (Weide et al., 2009; Orlandi et al., 2011; Aurisicchio and Ciliberto, 2012).”
BackgroundBenteyn, D., Anguille, S., Lint, S. V., Heirman, C., Nuffel, A. M. T. V., Corthals, J., Ochsenreither, S., Waelput, W., Beneden, K. V., Breckpot, K., et al. (2013) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2013.54 · Cited by 44
RNA Therapeutics: How Far Have We Gone?
Coutinho, M. F., Matos, L., Santos, J. I., & Alves, S. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-19966-1_7 · Cited by 45
Engineered mRNA Delivery Systems for Biomedical Applications
Wang, J., Zhu, H., Gan, J., Liang, G., Li, L., & Zhao, Y. (2023) · Advanced Materials · doi:10.1002/adma.202308029 · Cited by 46
mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446
Bell, G. D., Yang, Y., Leung, E. Y., & Krissansen, G. W. (2018) · PLoS ONE · doi:10.1371/journal.pone.0201464 · Cited by 44
mRNA vaccination as a safe approach for specific protection from type I allergy
Weiss, R., Scheiblhofer, S., Roesler, E., Weinberger, E., & Thalhamer, J. (2012) · Expert Review of Vaccines · doi:10.1586/erv.11.168 · Cited by 42
Mutanome Engineered RNA Immunotherapy: Towards Patient-Centered Tumor Vaccination
Vormehr, M., Schrörs, B., Boegel, S., Löwer, M., Türeci, Ö., & Şahin, U. (2015) · Journal of Immunology Research · doi:10.1155/2015/595363 · Cited by 44
Mannosylated and Histidylated LPR Technology for Vaccination with Tumor Antigen mRNA
Pichon, C., & Midoux, P. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-260-5_16 · Cited by 42
Functional differences between protamine preparations for the transfection of mRNA
Jarzębska, N. T., Läuchli, S., Iselin, C., French, L. E., Johansen, P., Guenova, E., Kündig, T. M., & Pascolo, S. (2020) · Drug Delivery · doi:10.1080/10717544.2020.1790692 · Cited by 42
“…are frequently used to package nucleic acids (antisense, siRNA, immunostimulatory nucleic acids, plasmid DNA, or messenger RNA) (Hoerr et al., 2000; Scheel et al., 2005; Vighi et al., 2012; Weide et al., 2009; Feyerabend et al., 2009), and several such formulations are in clinical trials.”
BackgroundSelf-citationTherapeutic Delivery of mRNA: The Medium Is the Message
McIvor, R. S. (2011) · Molecular Therapy · doi:10.1038/mt.2011.67 · Cited by 41
Breakthrough concepts in immune-oncology: Cancer vaccines at the bedside
Roy, S., Sethi, T. K., Taylor, D., Kim, Y. J., & Johnson, D. B. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.5bt0420-585rr · Cited by 44
Delivery of synthetic mRNAs for tissue regeneration
Steinle, H., Weber, M., Stoppelkamp, S., Große‐Berkenbusch, K., Golombek, S., Weber, M., Çanak-Ipek, T., Trenz, S.-M., Schlensak, C., & Avci‐Adali, M. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114007 · Cited by 42
Haen, S. P., & Rammensee, H. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.03.007 · Cited by 40
Self-citationDeyhimfar, R., Izady, M., Shoghi, M., Kazazi, M. H., Ghazvini, Z. F., Nazari, H., Fekrirad, Z., & Arefian, E. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e26971 · Cited by 42
Evolution and Progress of mRNA Vaccines in the Treatment of Melanoma: Future Prospects
Bafaloukos, D. I., Gazouli, I., Koutserimpas, C., & Samonis, G. (2023) · Vaccines · doi:10.3390/vaccines11030636 · Cited by 44
“Direct intradermal administration of protamine-stabilized mRNA encoding for melanoma antigens (Melan-A, Tyrosinase, gp100, MAGE-A1, MAGE-A3, Survivin) to 21 metastatic melanoma patients [42] was well-tolerated, inducing no adverse events of grade 3 or higher.”
Modified mRNA as a therapeutic tool to induce cardiac regeneration in ischemic heart disease
Hadas, Y., Katz, M. G., Bridges, C. R., & Zangi, L. (2016) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1367 · Cited by 37
DeFrancesco, L. (2017) · Nature Biotechnology · doi:10.1038/nbt.3812 · Cited by 40
de Jong, W., Leal, L., Buyze, J., Pannus, P., Guardo, A. C., Salgado, M., Mothe, B., Moltó, J., Morón‐López, S., Gálvez, C., et al. (2019) · Vaccines · doi:10.3390/vaccines7040209 · Cited by 37
Promising RNA-based cancer gene therapy using extracellular vesicles for drug delivery
Xue, V. W., Wong, S. C. C., Song, G., & Cho, W. C. S. (2020) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2020.1738377 · Cited by 37
“city, which is a good alternative for naked mRNA in cancer vaccination [95,96].”
BackgroundRegulatory Considerations on the Development of mRNA Vaccines
Naik, R., & Peden, K. (2020) · Current topics in microbiology and immunology · doi:10.1007/82_2020_220 · Cited by 37
Aarntzen, E. H. J. G., de Vries, I. J. M., Goertz, J., Beldhuis-Valkis, M., Brouwers, H. M. L. M., van de Rakt, M. W. M. M., Molen, R. G. V. D., Punt, C. J. A., Adema, G. J., Tacken, P. J., et al. (2012) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-012-1263-z · Cited by 37
“KLH is added to the vaccine both as a nonspecific T helper cell stimulus and to facilitate monitoring of the vaccineinduced immune responses [8–10].”
BackgroundDemystifying mRNA vaccines: an emerging platform at the forefront of cryptic diseases
Rouf, N. Z., Biswas, S., Tarannum, N., Oishee, L. M., & Muna, M. M. (2022) · RNA Biology · doi:10.1080/15476286.2022.2055923 · Cited by 39
Nanoformulations targeting immune cells for cancer therapy: mRNA therapeutics
Yang, W., Cao, J., Cheng, H., Chen, L., Yu, M., Chen, Y., & Cui, X. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.11.014 · Cited by 36
“The first clinical trial of mRNA cancer vaccine delivered by protamine was initiated by Benjamin and co-workers in 2004 [91], revealing that protamine was a safe mRNA delivery system and was able to induce T cell immunity.”
mRNA delivery via non-viral carriers for biomedical applications
Shuai, Q., Zhu, F., Zhao, M., & Yan, Y. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.121020 · Cited by 35
Combining oncolytic virotherapy and tumour vaccination
Bridle, B. W., Hanson, S. J., & Lichty, B. D. (2010) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2010.02.009 · Cited by 34
“Adjuvanted peptide, DNA, cell- and vector-based and even mRNA vaccines are all under investigation for the treatment of both leukemias and many types of solid tumours (for example [19,27–32]).”
BackgroundActivation of Innate Immunity by Therapeutic Nucleic Acids
Bishani, A., & Chernolovskaya, E. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413360 · Cited by 35
“Naked nucleic acids are not stable in the blood or body fluids or inside cells due to nuclease degradation, and in order to deliver them to endosomes, where nucleic acid sensing TLRs are located, they should be protected, thus encapsulation was used to form lipopolyplexes [158].”
BackgroundThe Current Landscape of mRNA Vaccines Against Viruses and Cancer–A Mini Review
Ladak, R. J., He, A. J., Huang, Y.-H., & Ding, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.885371 · Cited by 35
Advances and prospects of mRNA vaccines in cancer immunotherapy
Liu, Y., Yan, Q., Zeng, Z., Fan, C., & Xiong, W. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.189068 · Cited by 33
Emerging advances in delivery systems for mRNA cancer vaccines
Jiang, Z., Xu, Y., Du, G., & Sun, X. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.04.039 · Cited by 35
RNA pulsed dendritic cells: An approach for cancer immunotherapy
Garg, N. K., Dwivedi, P., Prabha, P. S., & Tyagi, R. K. (2013) · Vaccine · doi:10.1016/j.vaccine.2012.12.027 · Cited by 35
Multifunctional Immunoadjuvants for Use in Minimalist Nucleic Acid Vaccines
Abbasi, S., & Uchida, S. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13050644 · Cited by 33
“Natural and semi-synthetic polymers Protamine TLR 7/8 activation 1, 2, 3 [98,99] Chitosan STING pathway activation 1, 2, 3 [100–102] Dextran sulfate Uptake by lymphocytes 1, 2 [103] Cyclodextrins Lipid raft formation 1 [104,105]”
BackgroundProphylactic mRNA vaccination against allergy
Weiss, R., Scheiblhofer, S., Roesler, E., Ferreira, F., & Thalhamer, J. (2010) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0b013e32833fd5b6 · Cited by 33
Laila, U. E., An, W., & Xu, Z.-X. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1448489 · Cited by 34
Novel Vectors and Administrations for mRNA Delivery
Bai, C., Wang, C., & Lu, Y. (2023) · Small · doi:10.1002/smll.202303713 · Cited by 32
Bioinspired Spatiotemporal Management toward RNA Therapies
Ma, Y., Li, S., Lin, X., & Chen, Y. (2023) · ACS Nano · doi:10.1021/acsnano.3c08219 · Cited by 32
New challenges in therapeutic vaccines against HIV infection
Leal, L., Lucero, C., Gatell, J. M., Gallart, T., Plana, M., & García, F. (2017) · Expert Review of Vaccines · doi:10.1080/14760584.2017.1322513 · Cited by 33
Rahman, M. M., Zhou, N., & Huang, J. (2021) · Vaccines · doi:10.3390/vaccines9030244 · Cited by 32
“[28] reported the efficiency of protamine/mRNA complex by experimental analysis of intradermally-inoculated protamine/mRNAs complex that encodes for a variety of enzymes, such as Tyrosinase (an enzyme that helps to catalyze melanin formation), Melan-A (a melanoma antigen), gp100 (a protein included in the maturation o…”
BackgroundInfluentialmRNA-based modalities for infectious disease management
Zhang, M., Hussain, A., Yang, H., Zhang, J., Liang, X., & Huang, Y. (2022) · Nano Research · doi:10.1007/s12274-022-4627-5 · Cited by 35
Path towards mRNA delivery for cancer immunotherapy from bench to bedside
Chen, W., Zhu, Y., He, J., & Sun, X. (2023) · Theranostics · doi:10.7150/thno.89247 · Cited by 33
“Protamine-formulated mRNA vaccines, known as RNActive® vaccines, have been extensively studied in several clinical trials [142, 143].”
BackgroundTanaka, M., Butler, M. O., Ansén, S., Imataki, O., Berezovskaya, A., Nadler, L. M., & Hirano, N. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3083 · Cited by 29
“full-length Survivin mRNA have been conducted (11-13).”
The notorious R.N.A. in the spotlight - drug or target for the treatment of disease
Reautschnig, P., Vogel, P., & Stafforst, T. (2016) · RNA Biology · doi:10.1080/15476286.2016.1208323 · Cited by 30
“It was found that complexation of IVT-mRNA with protamine enhances immunogenicity via TLR-7 activation and simultaneously improves stability, however, with the downside of low antigen expression.(203) Anyway, a combination of protamine-complexed IVT-mRNA together with naked IVT-mRNA of the same sequence turned out to…”
BackgroundMbatha, L. S., Maiyo, F., & Singh, M. (2018) · Acta Pharmaceutica · doi:10.2478/acph-2019-0008 · Cited by 29
Advancing personalized medicine in brain cancer: exploring the role of mRNA vaccines
Lin, F., Lin, E. Z., Anekoji, M., Ichim, T. E., Hu, J. K., Marincola, F. M., Jones, L. D., Kesari, S., & Ashili, S. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04724-0 · Cited by 28
“In a phase I/II trial, Weide et al. [63] admonished pro-tamine-stabilized mRNAs coding for Melan-A, Tyrosi-nase, gp100, Mage-A1, Mage-A3, and Survivin to 21 metastatic melanoma patients.”
BackgroundmRNA-based therapeutic strategies for cancer treatment
Taibi, T., Cheon, S., Perna, F., & Vu, L. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.04.035 · Cited by 31
Advances in Nonviral mRNA Delivery Materials and Their Application as Vaccines for Melanoma Therapy
Neill, B., Romero, A. R., & Fenton, O. S. (2023) · ACS Applied Bio Materials · doi:10.1021/acsabm.3c00721 · Cited by 31
Have mRNA vaccines sentenced DNA vaccines to death?
Cagigi, A., & Douradinha, B. G. (2023) · Expert Review of Vaccines · doi:10.1080/14760584.2023.2282065 · Cited by 30
“Examples of carriers include cationic peptides like protamine [58], and various types of biodegradable ionizable LNPs [25,59–61].”
BackgroundZhou, J., Li, Y., Chen, S., & Deng, A. (2011) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-30-2 · Cited by 28
“MAGE-A1, MAGE-A3/4 and NY-ESO-1 were selected considering that these antigens have been well-accredited and are being applied for clinical trials of vaccine immunotherapy [15-18].”
BackgroundIge, M. A., Ren, X., Yang, Y., Zhang, H., Shen, C., Jiang, Y., Li, J., & Wan, X. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102721 · Cited by 30
Sköld, A. E., Mathan, T. S. M., van Beek, J. J. P., Flórez‐Grau, G., van den Beukel, M. D., Sittig, S. P., Wimmers, F., Bakdash, G., Schreibelt, G., & de Vries, I. J. M. (2018) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-018-2204-2 · Cited by 28
Metadata
- Authors
- Weide, B., Pascolo, S., Scheel, B., Derhovanessian, E., Pflugfelder, A., Eigentler, T. K., Pawelec, G., Hoerr, I., Rammensee, H.-G., & Garbe, C.
- Affiliations
- University of Tübingen (DE)
- CureVac (Germany) (DE)
- Corresponding author
- Weide, Benjamin
- Pflugfelder, Annette
- Eigentler, Thomas K.
- Garbe, Claus
- ORCID
- Venue
- Journal of Immunotherapy
- Published
- 2009-06
- Volume
- 32
- Issue
- 5
- Pages
- 498-507
- ISSN
- 1524-9557 (ISSN-L)
- OpenAlex
- W1966322307
- Cited by
- 378
- References
- 28
- Citations by year
- 2026: 15 · 2025: 31 · 2024: 29 · 2023: 45 · 2022: 45 · 2021: 40 · 2020: 22 · 2019: 14 · 2018: 19 · 2017: 16 · 2016: 14 · 2015: 16 · 2014: 17 · 2013: 12 · 2012: 13
- FWCI
- 6.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Immunotherapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Keywords
- mRNA vaccination, metastatic melanoma, tumor-associated antigens, Melan-A, tyrosinase, gp100, MAGE-1, MAGE-A3, survivin, keyhole limpet hemocyanin, GM-CSF, regulatory T cells, myeloid-derived suppressor cells, antitumor immunity, vaccine safety, complete response
- MeSH terms
- Adolescent, Adult, Aged, Antigens, Neoplasm, Bone Neoplasms, Feasibility Studies, Female, Hemocyanins, HLA-DR Antigens, Humans, Injections, Intradermal, Lung Neoplasms, Male, Melanoma, Middle Aged, Neoplasm Proteins, Neoplasm Staging, Protamines, Remission Induction, RNA, Messenger, CD4 Antigens, Granulocyte-Macrophage Colony-Stimulating Factor, Immunotherapy, Active, Cancer Vaccines, Myeloid Cells, CD11b Antigen, Cell Proliferation, T-Lymphocytes, Regulatory, Forkhead Transcription Factors, Melanoma-Specific Antigens
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