Long-term survival correlates with immunological responses in renal cell carcinoma patients treated with mRNA-based immunotherapy

Rittig, Susanne M; Haentschel, Maik; Weimer, Katrin J; Heine, Annkristin; Müller, Martin; Brugger, Wolfram; Horger, Marius; Maksimovic, Olga; Stenzl, Arnulf; Hoerr, Ingmar; Rammensee, Hans‐Georg; Holderried, Tobias A. W.; Kanz, Lothar; Pascolo, Steve; Brossart, Peter

doi:10.1080/2162402x.2015.1108511

Cited by 46 publications

(35 citation statements)

References 31 publications

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“…Owing to this and their unsurpassed inherent safety features, this type of genetic vaccine has been repeatedly employed in clinical trials mainly in the cancer field. So far, immunotherapy with mRNA has been performed in patients suffering from melanoma, non‐small‐cell lung cancer, renal cell carcinoma, and prostate cancer . Recently, a protective mRNA vaccine against rabies was successfully tested in healthy subjects .…”

Section: Tailor‐made Genetic Vaccinesmentioning

confidence: 99%

DNA and mRNA vaccination against allergies

Scheiblhofer

Thalhamer

Weiss

2018

Pediatric Allergy Immunology

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Allergen‐specific immunotherapy, which is performed by subcutaneous injection or sublingual application of allergen extracts, represents an effective treatment against type I allergic diseases. However, due to the long duration and adverse reactions, only a minority of patients decides to undergo this treatment. Alternatively, early prophylactic intervention in young children has been proposed to stop the increase in patient numbers. Plasmid DNA and mRNA vaccines encoding allergens have been shown to induce T helper 1 as well as T regulatory responses, which modulate or counteract allergic T helper 2–biased reactions. With regard to prophylactic immunization, additional safety measurements are required. In contrast to crude extracts, genetic vaccines provide the allergen at high purity. Moreover, by targeting the encoded allergen to subcellular compartments for degradation, release of native allergen can be avoided. Due to inherent safety features, mRNA vaccines could be the candidates of choice for preventive allergy immunizations. The subtle priming of T helper 1 immunity induced by this vaccine type closely resembles responses of non‐allergic individuals and—by boosting via natural allergen exposure—could suffice for long‐term protection from type I allergy.

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Section: Tailor‐made Genetic Vaccinesmentioning

confidence: 99%

DNA and mRNA vaccination against allergies

Scheiblhofer

Thalhamer

Weiss

2018

Pediatric Allergy Immunology

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“…22 Clinical experience with mRNA vaccines, so far, is very positive: No severe side effects have been reported, and an antigen specific immune response could be detected in some patients. 23–26 We are only aware of one clinical study involving lipid nanoparticles as an mRNA vector that reported results and of one ongoing study. 20,27 …”

mentioning

confidence: 99%

Lipid Nanoparticle Assisted mRNA Delivery for Potent Cancer Immunotherapy

Oberli¹,

Reichmuth²,

Dorkin³

et al. 2016

Nano Lett.

561

486

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The induction of a strong cytotoxic T cell response is an important prerequisite for successful immunotherapy against many viral diseases and tumors. Nucleotide vaccines, including mRNA vaccines with their intracellular antigen synthesis, have been shown to be potent activators of a cytotoxic immune response. The intracellular delivery of mRNA vaccines to the cytosol of antigen presenting immune cells is still not sufficiently well understood. Here, we report on the development of a lipid nanoparticle formulation for the delivery of mRNA vaccines to induce a cytotoxic CD 8 T cell response. We show transfection of dendritic cells, macrophages, and neutrophils. The efficacy of the vaccine was tested in an aggressive B16F10 melanoma model. We found a strong CD 8 T cell activation after a single immunization. Treatment of B16F10 melanoma tumors with lipid nanoparticles containing mRNA coding for the tumor-associated antigens gp100 and TRP2 resulted in tumor shrinkage and extended the overall survival of the treated mice. The immune response can be further increased by the incorporation of the adjuvant LPS. In conclusion, the lipid nanoparticle formulation presented here is a promising vector for mRNA vaccine delivery, one that is capable of inducing a strong cytotoxic T cell response. Further optimization, including the incorporation of different adjuvants, will likely enhance the potency of the vaccine.

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“…In both cases, an adapted mixture of six defined ivt mRNAs, coding adequate tumor antigens, was intradermally injected: naked for the renal cell carcinoma patients and complexed with Protamine for the melanoma patients. Both of the studies have indicated that the ivt mRNA vaccine formulations are safe, induce immune responses, and some clinical responses were reported [ 11 , 13 , 19 ].…”

Section: History Of Synthetic Non-replicating Mrna Vaccinesmentioning

confidence: 99%

Synthetic Messenger RNA-Based Vaccines: From Scorn to Hype

Pascolo

2021

Viruses

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In the race for a vaccine against SARS-CoV-2, the synthetic mRNA format has been shown to be the fastest one and proved to be safe and highly efficient, even at the very low dose of a few µg per injection. The mRNA vaccines are not new: vaccines that are based on attenuated mRNA viruses, such as Mumps, Measles, and Rubella, immunize by delivering their mRNAs into the cells of the vaccinated individual, who produces the viral proteins that then prime the immune response. Synthetic mRNA in liposomes can be seen as a modern, more refined, and thereby a safer version of those live attenuated RNA viruses. The anti-COVID-19 mRNA vaccine (coding the SARS-CoV-2 spike protein) is the third synthetic RNA therapeutic being approved. It follows the aptamer Macugen® (which neutralizes VEGF) and the siRNA Onpattro® (which destroys the transthyretin-coding mRNA). Remarkably, the 30 µg of mRNA that are contained in the first approved anti-COVID-19 vaccine are sufficient for generating high levels of neutralizing antibodies against the virus in all injected volunteers (including participants over 65 years old). The efficacy and safety data are stunning. The distribution of these vaccines throughout the world will bring a halt to the coronavirus pandemic.

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Long-term survival correlates with immunological responses in renal cell carcinoma patients treated with mRNA-based immunotherapy

Cited by 46 publications

References 31 publications

DNA and mRNA vaccination against allergies

DNA and mRNA vaccination against allergies

Lipid Nanoparticle Assisted mRNA Delivery for Potent Cancer Immunotherapy

Synthetic Messenger RNA-Based Vaccines: From Scorn to Hype

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