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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]
Citations
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
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Items 201–300 of 378
Li, M., Wang, Z., Xie, C., & Xia, X. (2022) · International review of cytology · doi:10.1016/bs.ircmb.2022.04.011 · Cited by 30
Antigen transfer and its effect on vaccine-induced immune amplification and tolerance
Shi, Y., Lu, Y., & You, J. (2022) · Theranostics · doi:10.7150/thno.75904 · Cited by 27
“Dermal APCs (such as cDCs, mo-DCs, LCs and macrophages) [224] and lymphatic system facilitate a quick and effective initiation of immune response, conferring dermis a highly immunocompetent site for vaccine delivery [225, 226].”
BackgroundApplication of mRNA Technology in Cancer Therapeutics
Eralp, Y. (2022) · Vaccines · doi:10.3390/vaccines10081262 · Cited by 27
“Early clinical studies of naked mRNA fortified with protamine stabilization showed a favorable immune response in 50% of the cohort comprising seven patients with melanoma, and a complete clinical response in one patient [101].”
BackgroundVizirianakis, I. S., Miliotou, Α. N., Mystridis, G. A., Andriotis, E. G., Andreadis, I. I., Papadopoulou, L. C., & Fatouros, D. G. (2019) · Expert Review of Precision Medicine and Drug Development · doi:10.1080/23808993.2019.1605828 · Cited by 25
Chung, S., Lee, C. M., & Zhang, M. (2022) · Nanoscale Horizons · doi:10.1039/d2nh00289b · Cited by 28
Clinical advancements in mRNA vaccines against viral infections
Fatima, M. T., Park, P., & Hong, K. (2024) · Clinical Immunology · doi:10.1016/j.clim.2024.110424 · Cited by 25
Lu, Y., Qian, C., Huang, Y., Ren, T., Xie, W., Xia, N., & Li, S. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.145501 · Cited by 28
Loomis, K. H., Kirschman, J. L., Bhosle, S. M., Bellamkonda, R. V., & Santangelo, P. J. (2015) · Journal of Materials Chemistry B · doi:10.1039/c5tb01753j · Cited by 24
In the Era of mRNA Vaccines, Is There Any Hope for HIV Functional Cure?
Esteban, I., Pastor-Quiñones, C., Usero, L., Plana, M., García, F., & Leal, L. (2021) · Viruses · doi:10.3390/v13030501 · Cited by 26
Emerging Progress of RNA-Based Antitumor Therapeutics
Fu, J., Dong, H., Wu, J., & Jin, Y. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.83732 · Cited by 23
“Several milestone events in RNA-based antitumor treatment are shown in Figure 2 [7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19].”
BackgroundAdvances in targeted delivery of mRNA into immune cells for enhanced cancer therapy
Huang, L., Huang, Z., Zhang, Y., Lin, C., Zhao, Z., Li, R., Saw, P. E., & Xu, X. (2024) · Theranostics · doi:10.7150/thno.93745 · Cited by 24
“Subsequently, an increasing number of clinical trials of mRNA vaccines are underway, such as NCT00204607 and NCT02316457[24].”
BackgroundVaccines against COVID-19: Priority to mRNA-Based Formulations
Pascolo, S. (2021) · Cells · doi:10.3390/cells10102716 · Cited by 23
Self-citationThe expression, function, and utilization of Protamine1: a literature review
Ren, S., Chen, X., Tian, X., Yang, D., Dong, Y., Chen, F., & Fang, X. (2021) · Translational Cancer Research · doi:10.21037/tcr-21-1582 · Cited by 23
“The protamine-mRNA vaccine coding tumor-associated antigens was constructed to induce antitumor immune responses, and has achieved satisfactory effects on melanoma patients (26).”
BackgroundMethodCao, L., Yu, Y.-F., Li, Z., Zhong, N., Wang, G.-R., Xiao, Y., Liu, B., Wu, Q., Feng, C., & Bu, L. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02590-6 · Cited by 28
Advancements in RNA-based therapies from bench to bedside
Singh, A., Tekade, M., Nagaraja, S., Bharti, A., & Tekade, R. K. (2026) · npj Drug Discovery. · doi:10.1038/s44386-025-00037-y · Cited by 24
“Protamine-protected mRNAs encoding tumor-associated antigens were used in these vaccines, and the outcomes demonstrated an increase in vaccine-directed T cells, suggesting a possible therapeutic bene fi t 25 .”
Addressing COVID-19 vaccine hesitancy
Kassianos, G. C., Puig‐Barberà, J., Dinse, H., Teufel, M., Türeci, Ö., & Pather, S. (2022) · Drugs in Context · doi:10.7573/dic.2021-12-3 · Cited by 22
mRNA delivery technologies: Toward clinical translation
Gómez-Aguado, I., Rodríguez-Castejón, J., Beraza-Millor, M., Rodríguez‐Gascón, A., del Pozo‐Rodríguez, A., & Solinís, M. Á. (2022) · International review of cytology · doi:10.1016/bs.ircmb.2022.04.010 · Cited by 23
Development of mRNA vaccines and their prophylactic and therapeutic applications
Lee, K., Kim, M., Seo, Y., & Lee, H. (2018) · Nano Research · doi:10.1007/s12274-018-2095-8 · Cited by 23
Zohra, F. T., Maitani, Y., & Akaike, T. (2012) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.35.111 · Cited by 21
Antitumor Vaccination with Synthetic mRNA: Strategies for In Vitro and In Vivo Preclinical Studies
Diken, M., Kreiter, S., Selmi, A., Türeci, Ö., & Şahin, U. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-260-5_15 · Cited by 19
mRNA-based therapies: Preclinical and clinical applications
Qureischi, M., Mohr, J., Arellano-Viera, E., Knudsen, S. E., Vohidov, F., & Garitano-Trojaola, A. (2022) · International review of cytology · doi:10.1016/bs.ircmb.2022.04.007 · Cited by 21
Li, H., Liu, T., Tu, Z., Xie, C., Wen, W., & Sun, W. (2022) · Biomolecules · doi:10.3390/biom13010090 · Cited by 20
The Safety and Effectiveness of mRNA Vaccines Against SARS-CoV-2
Jamous, Y. F., & Alhomoud, D. A. (2023) · Cureus · doi:10.7759/cureus.45602 · Cited by 24
“Protamine is a natural cationic peptide that can be used for the encapsulation of the mRNA vaccine [27].”
BackgroundGu, J., Xu, Z., Liu, Q., Tang, S., Zhang, W., Xie, S., Chen, X., Chen, J., Yong, K., Yang, C., et al. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202302409 · Cited by 20
Profile of Katalin Karikó and Drew Weissman: 2023 Nobel laureates in Physiology or Medicine
Krammer, F., & Palese, P. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2400423121 · Cited by 19
Ballout, A. A., Babaie, A., Kolesnik, M., Li, J. Y., Hameed, N., Waldman, G., Chaudhry, F., Saba, S., Harel, A., & Najjar, S. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.796882 · Cited by 18
Immune Signatures and Survival of Patients With Metastatic Melanoma, Renal Cancer, and Breast Cancer
Wistuba‐Hamprecht, K., Gouttefangeas, C., Weide, B., & Pawelec, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01152 · Cited by 17
Self-citationmRNA: Delivering an Antitumor Message?
Lint, S. V., Thielemans, K., & Breckpot, K. (2011) · Immunotherapy · doi:10.2217/imt.11.28 · Cited by 17
mRNA vaccine development and applications: A special focus on tumors (Review)
Chen, B., Yang, Y., Wang, X., Yang, W., Lu, Y., Wang, D., Zhuo, E., Tang, Y., Su, J., Tang, G., et al. (2024) · International Journal of Oncology · doi:10.3892/ijo.2024.5669 · Cited by 17
“In addition, 1 of the 7 patients with measurable disease showed a complete response to the vaccine (169).”
BackgroundOptimal delivery strategies for nanoparticle-mediated mRNA delivery
Li, X., Guo, X., Hu, M., Cai, R., & Chen, C. (2023) · Journal of Materials Chemistry B · doi:10.1039/d2tb02455a · Cited by 16
Ye, Z., Li, Z., Jin, H., & Qian, Q. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-94-017-7555-7_3 · Cited by 16
Therapeutic Mechanism of Nucleic Acid Drugs
Liu, L., Gao, H., Guo, C., Liu, T., Li, N., & Qian, Q. (2021) · ChemistrySelect · doi:10.1002/slct.202002901 · Cited by 16
FoxP3 and indoleamine 2,3-dioxygenase immunoreactivity in sentinel nodes from melanoma patients
Ryan, M. A., Crow, J., Kahmke, R. R., Fisher, S. R., Su, Z., & Lee, W. T. (2014) · American Journal of Otolaryngology · doi:10.1016/j.amjoto.2014.08.009 · Cited by 16
“[19] Weide B, Pascolo S, Scheel B, et al.”
BackgroundCancer vaccines: Discovery, development, and challenges for clinical translation
Zhang, Z., Yao, S., Wang, Y., Luo, K., Amiji, M. M., & Anderson, K. C. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123615 · Cited by 15
Making the Next Generation of Therapeutics: mRNA Meets Synthetic Biology
Hınçer, A., Ahan, R. E., Aras, E., & Şeker, U. Ö. Ş. (2023) · ACS Synthetic Biology · doi:10.1021/acssynbio.3c00253 · Cited by 15
The mRNA vaccine platform for veterinary species
Fazel, F., Doost, J. S., Raj, S., Boodhoo, N., Karimi, K., & Sharif, S. (2024) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2024.110803 · Cited by 19
Sayour, E. J., Sanchez-Perez, L. A., Flores, C., & Mitchell, D. A. (2015) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-015-0058-0 · Cited by 15
“In a phase I/II trial for patients with metastatic melanoma, intradermal injection of protamine-stabilized mRNAs coding for melanoma antigens was shown to be safe and feasible with one complete remission [75].”
BackgroundGeneration of Immunostimulating 130 nm Protamine–RNA nanoparticles
Tusup, M., & Pascolo, S. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6481-9_9 · Cited by 15
Self-citationMen, K., Zhang, R., Zhang, X., Huang, R., Zhu, G., Tong, R., Yang, L., Wei, Y., & Duan, X. (2018) · RSC Advances · doi:10.1039/c7ra13656k · Cited by 15
Recent Advances in Messenger Ribonucleic Acid (mRNA) Vaccines and Their Delivery Systems: A Review
Belay, W. Y., Nibret, G., & Aschale, Y. (2023) · Clinical Pharmacology Advances and Applications · doi:10.2147/cpaa.s418314 · Cited by 16
“Hence, it was utilized in the development of the self-adjuvanted RNActive vaccination platform, which has proven effective against several infectious illnesses and malignancies.(115,156,158,159) Furthermore, protamine protects mRNA from being degraded by serum RNases(151) and is found to guard against severe storage c…”
Cancer/Testis Antigens as Targets for RNA-Based Anticancer Therapy
Shim, K., Jo, H., & Jeoung, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914679 · Cited by 14
“…of forkhead Box P3+ (Foxp3+)/CD4+ regulatory T cells and Myeloid-derived suppressor cells (MDSCs) in metastatic melanoma patients [91]. mRNAs encoding melan-A, tyrosinase, gp100, MAGE-A1, MAGE-A3, and survivin increase vaccine-specific T cells in two of four immunologically evaluable patients [91].”
InfluentialIn Vitro Synthesis of Modified RNA for Cardiac Gene Therapy
Sultana, N., Sharkar, M. T. K., Hadas, Y., Chepurko, E., & Zangi, L. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0668-1_21 · Cited by 14
Zeng, Q., Zhang, S., Leng, N., & Xing, Y. (2024) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2024.104576 · Cited by 13
mRNA vaccine development for cholangiocarcinoma: a precise pipeline
Tang, T., Huang, X., Zhang, G., Lu, M., & Liang, T. (2022) · Military Medical Research · doi:10.1186/s40779-022-00399-8 · Cited by 13
“A, Tyrosinase, Survivin, and gp100 Protamine‑protected GM‑CSF s.c Melanoma 20 Antigen‑specific T cells detected in 2/4 evaluable patients; 1 CR observed in 7 patients NCT00204607 [41] hTERT DC – Acute myeloid leu‑ kemia 21 11 patients (58”
BackgroundGehrcken, L., Sauerer, T., Schaft, N., & Dörrie, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168679 · Cited by 13
“They showed a decrease in regulatory T-cells and an increase in vaccine-directed T-cells [98].”
BackgroundProcess and analytical strategies for the safe production of mRNA vaccines and therapeutics
Nowak, C. J. A., Liu, S., Falconer, R. J., & Gerstweiler, L. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-11455-0 · Cited by 16
Chatterjee, S., Bhattacharya, M., Lee, S., & Chakraborty, C. (2023) · Current Research in Biotechnology · doi:10.1016/j.crbiot.2023.100150 · Cited by 12
Assembling the RNA therapeutics toolbox
Teng, M., Xia, Z. J., Lo, N., Daud, K., & He, H. H. (2024) · Medical Review · doi:10.1515/mr-2023-0062 · Cited by 12
“During the 2000s, the importance of pseu-douridine modi fi cation on mRNA was recognized and the fi rst human trial of an mRNA vaccine against melanoma was initiated [9, 10].”
BackgroundThe legacy of mRNA engineering: A lineup of pioneers for the Nobel Prize
Janowski, M., & Andrzejewska, A. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.07.003 · Cited by 12
Synthetic mRNA: Production, Introduction into Cells, and Physiological Consequences
Rhoads, R. E. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3625-0_1 · Cited by 11
Potential Application of Modified mRNA in Cardiac Regeneration
Wang, A. Y. L., Chang, Y., Chen, K., & Loh, C. Y. Y. (2024) · Cell Transplantation · doi:10.1177/09636897241248956 · Cited by 12
Therapeutic mRNA vaccine applications in oncology
Elliott, L. A., Foster, T. P., Castillo, P., Méndez-Gómez, H., & Sayour, E. J. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.04.044 · Cited by 11
A Commotion in the Skin: Developing Melanoma Immunotherapies
Brenner, E., & Röcken, M. (2022) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2022.01.025 · Cited by 11
Clinical benefit and safety associated with mRNA vaccines for advanced solid tumors: A meta‐analysis
Zhang, T., Xu, H., Zheng, X., Xiong, X., Zhang, S., Yi, X., Li, J., Wei, Q., & Ai, J. (2023) · MedComm · doi:10.1002/mco2.286 · Cited by 10
Urbina, F., Morales, S., & Maldonado, E. (2020) · Polymers · doi:10.3390/polym12081633 · Cited by 11
Implications of mRNA-based SARS-CoV-2 vaccination for cancer patients
Romano, E., Pascolo, S., & Ott, P. A. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002932 · Cited by 11
Self-citationmRNA-Based Anti-TCR CDR3 Tumour Vaccine for T-Cell Lymphoma
Tusup, M., Läuchli, S., Jarzębska, N. T., French, L. E., Chang, Y., Eisenring, M., Su, A. A. H., Kündig, T. M., Guenova, E., & Pascolo, S. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13071040 · Cited by 12
Self-citationVaccines targeting angiogenesis in melanoma
Zahedipour, F., Zamani, P., Jamialahmadi, K., Jaafari, M. R., & Sahebkar, A. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174565 · Cited by 11
RNA Vaccines against Infectious Diseases: Vital Progress with Room for Improvement
Abdelzaher, H. M., Gabr, A. S., Saleh, B. M., Gawad, R. M. A., Nour, A. A., & Abdelnaser, A. (2021) · Vaccines · doi:10.3390/vaccines9111211 · Cited by 12
“They concluded that direct injection of protamine-protected mRNA is feasible, safe and capable of promoting antitumor immunity [20].”
BackgroundJiang, X., Liu, Y., Liu, D. X., Shi, J., & Langer, R. (2022) · Wiley eBooks · doi:10.1002/9781119000822.hfcm070.pub2 · Cited by 11
The mRNA-Based Innovative Strategy: Progress and Challenges
Zhou, H., Wei, D., Chen, Z., Chen, H., Dong, C., Cai, W., Wang, J., Liu, X., Li, Y., Yang, Y., et al. (2026) · Nano-Micro Letters · doi:10.1007/s40820-025-01906-x · Cited by 17
“Protamine, a mixture of natural cationic cell-penetrating peptides, is an early material for mRNA delivery [15, 150].”
The dawn of a new Era: mRNA vaccines in colorectal cancer immunotherapy
Song, J., Zhang, Y., Zhou, C., Zhan, J., Cheng, X., Huang, H., Mao, S., & Zong, Z. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112037 · Cited by 10
Eslami, S. M., & Lü, X. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.10.035 · Cited by 10
DeLong, R. K., & Curtis, C. B. (2016) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1415 · Cited by 10
Hoehn, S. J., Krul, S. E., Skory, B. J., & Crespo‐Hernández, C. E. (2021) · Chemistry - A European Journal · doi:10.1002/chem.202103667 · Cited by 9
Advantages and disadvantages of RNA therapeutics
Huy, B. L., Phuong, H. B. T., & Xuan, H. L. (2024) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2023.12.016 · Cited by 10
Szabó, I. L., Emri, G., Ladányi, A., & Tı́már, J. (2025) · Cancers · doi:10.3390/cancers17091422 · Cited by 11
“In an early phase I/II trial, patients with metastatic melanoma were treated intradermally with vaccines containing six melanoma antigens (MelanA, tyrosinase, gp100, MAGEA1/3, survivin), applying RNA protection with the cationic peptide protamin [96].”
Ye, L., Zhao, G., Ma, J., Gan, Q., Luo, N., Pan, D., Chen, C., Chen, X., & Ning, S. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02769-3 · Cited by 10
Wang, G., Gao, Y., Chen, Y., Wang, K., Zhang, S., & Li, G. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.921711 · Cited by 9
Emerging trends of research on mRNA vaccines: A co-citation analysis
Chen, J., Zhang, T., Lu, Y. Z., Yang, X., & Ouyang, Z. (2022) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2022.2110409 · Cited by 10
The mRNA Vaccine Heralds a New Era in Vaccinology
Shinde, K., Bendre, S., Kale, N., & Gilda, S. (2022) · Asian Journal of Pharmacy and Technology · doi:10.52711/2231-5713.2022.00042 · Cited by 9
Nurturing Deep Tech to Solve Social Problems: Learning from COVID-19 mRNA Vaccine Development
Okuyama, R. (2022) · Pathogens · doi:10.3390/pathogens11121469 · Cited by 11
“The mRNA vaccine was first administered to humans in 2009 aimed as a therapeutic vaccine for cancer [33].”
MethodLiu, Y., Liu, D. X., Shi, J., & Langer, R. (2017) · Wiley eBooks · doi:10.1002/9781119000822.hfcm070 · Cited by 9
RNA therapeutics in cardiovascular medicine
Damase, T. R., & Cooke, J. P. (2025) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000001210 · Cited by 8
“Subsequently, intradermal injection of protamine-stabilized protamine-stabilized mRNAs encoding melanoma-associated antigens induced a T-cell response in some individuals diagnosed with metastatic melanoma [17].”
Chien, K. R., Foo, K. S., & Witman, N. (2026) · Nature Reviews Drug Discovery · doi:10.1038/s41573-026-01459-7 · Cited by 12
“Prior to COVID-19, mRNA agents were being investigated as therapeutic vaccines in oncology 154–156 , based on the concept that they could promote recognition of antigens specifically expressed on cancer cells by the immune system to inhibit tumour progression or reduce the risk of recurrence…”
Characterization of KLH-driven immune responses in clinical studies: A systematic review
Saghari, M., Jansen, M. A. A., Grievink, H. W., Rißmann, R., & Moerland, M. (2022) · Frontiers in Drug Discovery · doi:10.3389/fddsv.2022.992087 · Cited by 8
The oral and craniofacial relevance of chemically modified RNA therapeutics.
Elangovan, S., Kormann, M. S. D., Khorsand, B., & Salem, A. K. (2016) · PubMed · Cited by 8
Musa, H. H., & Musa, T. H. (2022) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2022.2135927 · Cited by 11
Miliotou, Α. N., Foltopoulou, P. F., Ingendoh‐Tsakmakidis, A., Tsiftsoglou, A. S., Vizirianakis, I. S., Pappas, I. S., & Papadopoulou, L. C. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15010286 · Cited by 7
Accordino, G., Lettieri, S., Bortolotto, C., Benvenuti, S., Gallotti, A., Gattoni, E., Agustoni, F., Pozzi, E., Rinaldi, P., Primiceri, C., et al. (2020) · Cancers · doi:10.3390/cancers12082105 · Cited by 7
“Preclinical [191,192] and clinical studies [193,194] have demonstrated that DCs transfected with stabilized mRNA coding for tumor-associated antigen/whole tumor RNA can generate potent anticancer immune responses.”
BackgroundProbst, J., Fotin‐Mleczek, M., Schlake, T., Theß, A., Kramps, T., & Kallen, K. (2011) · Springer eBooks · doi:10.1007/978-3-7091-0439-2_11 · Cited by 7
Herberhold, S., Coch, C., Zillinger, T., Hommertgen, B., Busch, N., Schuberth, C., Hartmann, E., Wimmenauer, V., Hagmann, C. A., Lüdenbach, B., et al. (2011) · Antiviral Therapy · doi:10.3851/imp1822 · Cited by 7
“Protamine is already approved for therapeutic use in humans, and has been used safely and successfully for intracutaneous delivery of mRNA to TLR7 in dendritic cells of the skin in a Phase I/II clinical trial [32].”
BackgroundTowards customized cancer vaccines: a promising filed in personalized cancer medicine
Xu, X., Zhou, Z., Li, H., & Fan, Y. (2021) · Expert Review of Vaccines · doi:10.1080/14760584.2021.1909479 · Cited by 6
Tadic, S., Ochoa‐Callejero, L., Narro-Íñiguez, J., Garcı́a-Sanmartı́n, J., & Martı́nez, A. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1604156 · Cited by 9
Pascolo, S. (2023) · European Journal of Immunology · doi:10.1002/eji.202249941 · Cited by 6
Self-citationMakhijani, S., Elossaily, G. M., Rojekar, S. V., & Ingle, R. G. (2024) · Pharmaceutical Development and Technology · doi:10.1080/10837450.2024.2361656 · Cited by 7
“A protamine-based delivery platform for prostate cancer has been evaluated in clinical trials, melanoma, NSCLC, etc. (Weide et al. 2009; K € ubler et al. 2015; Papachristofilou et al. 2019; Zhang et al. 2020; Yu et al. 2023),.”
Diken, M., Kreiter, S., Kloke, B., & Şahin, U. (2015) · Progress in tumor research · doi:10.1159/000437184 · Cited by 6
Recent developments in cancer vaccines
Mukherjee, B., Hoque, A. A., Chakraborty, A., Chakraborty, S., Dutta, L., Dutta, D., Banerjee, S., Dhara, M., & Deepa, R. M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-823686-4.00018-5 · Cited by 6
Molekulare zielgerichtete Therapie und Immuntherapie des Prostatakarzinoms
Grüllich, C., Nößner, E., Pfister, D. J. K. P., & Grünwald, V. (2020) · Der Urologe · doi:10.1007/s00120-020-01198-6 · Cited by 6
RNA Vaccination Therapy: Advances in an Emerging Field
Kreiter, S., Diken, M., Pascolo, S., Nair, S. K., Thielemans, K., & Geall, A. J. (2016) · Journal of Immunology Research · doi:10.1155/2016/9703914 · Cited by 7
Self-citationCai, X., Zhang, X., & Bai, H. (2020) · OSF Preprints (OSF Preprints) · doi:10.31219/osf.io/ypgx4 · Cited by 6
Muodiaju, J. C., & Madu, C. S. (2025) · Cureus · doi:10.7759/cureus.84821 · Cited by 5
“Studies on COVID-19 mRNA vaccines indicate that antibody levels decline over time, prompting the need for booster doses to sustain protection against emerging variants [19].”
Transitional Insight into the RNA-Based Oligonucleotides in Cancer Treatment
Tabasi, H., Mollazadeh, S., Fazeli, E., Abnus, K., Taghdisi, S. M., Ramezani, M., & Alibolandi, M. (2023) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-023-04597-5 · Cited by 5
“To test the mRNA vaccine in another cancer, Weide et al. [147] injected protamine-stabilized mRNAs into 21 patients with metastatic melanoma, while in half of the cases, keyhole limpet hemo-cyanin (KLH) was added to the vaccine.”
Hydrated electrons and cluster science
Ahmadi, S. (2021) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2021.131898 · Cited by 6
Nair, S. K., Boczkowski, D., Pruitt, S. K., & Urban, J. H. (2011) · Informa Healthcare eBooks · doi:10.3109/9781841848303.016 · Cited by 5
Grigoruţă, M., Kong, X., & Qin, Y. W. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14145137 · Cited by 4
“Both unmodified (“naked”) mRNA and protamine-complexed mRNA formulations have demonstrated safety and moderate immunogenicity in early-phase studies, with antigen-specific immune responses observed in subsets of patients [137,138].”
Unraveling the potential: mRNA therapeutics in oncology
Gawalski, K., Przybyszewska, W., Hunia, J., Gawalska, A., & Rymarz, A. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1643444 · Cited by 6
Tan, T., Diao, Y., Yu, X., Chen, L., & Fang, H. (2026) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.12.044 · Cited by 8
mRNA and Peptide Vaccines in Melanoma—Current Landscape and Future Direction
Qin, J. J., Wang, Y., & Sandhu, S. (2026) · Cells · doi:10.3390/cells15040344 · Cited by 5
“Exogenous immunostim-ulants, including arginine-rich protamine peptides, may be added to vaccines to further activate TLR7/8 pathways, promoting B-and T-cell responses and suppressing circulating FoxP3+/CD4+ Treg cells, as demonstrated in an early-phase trial [62,63].”
Research and Clinical Progress of Therapeutic Tumor Vaccines
Dong, C., Zhuang, L., Tan, D., Sun, H., Liang, J., Wei, D., Zheng, Y., Zhang, L., Liu, S., Zhang, Y., et al. (2025) · Vaccines · doi:10.3390/vaccines13070672 · Cited by 5
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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