Results of the First Phase I/II Clinical Vaccination Trial With Direct Injection of mRNA

@article{Weide2008ResultsOT,
  title={Results of the First Phase I/II Clinical Vaccination Trial With Direct Injection of mRNA},
  author={Benjamin Weide and Jean-Philippe Carralot and A. Reese and Birgit Scheel and Thomas Kurt Eigentler and Ingmar Hoerr and Hans-Georg Rammensee and Claus Garbe and Steve Pascolo},
  journal={Journal of Immunotherapy},
  year={2008},
  volume={31},
  pages={180-188}
}
Vaccination against tumor antigens has been shown to be a safe and efficacious prophylactic and therapeutic antitumor treatment in many animal models. Clinical studies in humans indicate that specific immunotherapy can also result in clinical benefits. The active pharmaceutical ingredient in such vaccines can be DNA, RNA, protein, or peptide and can be administered naked, encapsulated, or after delivery in vitro into cells that are then adoptively transferred. One of the easiest, most versatile… 
View on Wolters Kluwer
ncbi.nlm.nih.gov
196 Citations
Highly Influential Citations
3
Background Citations
63
Methods Citations
7
Results Citations
3

196 Citations

mRNA Vaccination and Personalized Cancer Therapy
TLDR
This chapter provides a short summary of the history of mRNA-based vaccination and introduces into the design and production of mRNA vaccines, and provides insights into the preclinical development and clinical translation of personalized mRNA vaccines which are tailored to the antigen profile of individual cancer patients.
Intranasal vaccination with messenger RNA as a new approach in gene therapy: Use against tuberculosis
TLDR
Vaccination of mice with a single dose of naked mRNA-Hsp65 through intranasal route was able to induce protection against subsequent challenge with virulent strain of Mycobacterium tuberculosis, showing a novel and efficient strategy to control experimental tuberculosis.
Clinical and immunological effects of mRNA vaccines in malignant diseases
TLDR
This review will summarize the most recent technological developments and application of mRNA vaccines in clinical trials and discusses the results, challenges and future directions with a special focus on the induced innate and adaptive immune responses.
mRNA
TLDR
The use of ex vivo mRNA-modified DCs and “naked mRNA” for cancer immunotherapy focusing on parameters such as the employed DC subtype, DC activation stimulus and route of immunization is discussed.
Direct Injection of Protamine-protected mRNA: Results of a Phase 1/2 Vaccination Trial in Metastatic Melanoma Patients
TLDR
It is shown here that direct injection of protamine-protected mRNA is feasible and safe and 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 protamines-mRNA vaccine.
Plasmid DNA- and messenger RNA-based anti-cancer vaccination.
mRNA therapeutics in cancer immunotherapy
TLDR
This review highlights the advancements in the field of mRNA-based cancer therapeutics, providing insights into key preclinical developments and the evolving clinical landscape.
Intranodal vaccination with naked antigen-encoding RNA elicits potent prophylactic and therapeutic antitumoral immunity.
TLDR
In tumor-bearing mice intralymphatic RNA vaccination elicited protective and therapeutic antitumor immune responses, resulting in a remarkable survival benefit as compared with other treatment regimens.
Cancer vaccination by electro-gene-transfer
TLDR
Recent data showing initial evidence of immunogenicity by gene-electro-transfer in the clinic is reported and how new vector development combined with in vivo electroporation will allow nucleic acid vaccination to become a robust approach to fight cancer is discussed.
Opportunities and Challenges in the Delivery of mRNA-Based Vaccines
TLDR
Opportunities and challenges in the delivery of mRNA-based therapeutics with a focus on non-viral delivery systems are reviewed and perspectives on the future of this promising new type of medicine are highlighted.
...
...

References

SHOWING 1-10 OF 18 REFERENCES
Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines
TLDR
It is reported here that injection of naked β-globin untranslated region (UTR)-stabilized mRNA coding for β-galactosidase is followed by detectable translation in vivo, and it is shown that such a vaccination strategy primes a T helper 2 type of response which can be enhanced and shifted to a Th1-type immune response by application of recombinant granulocyte/macrophage colony-stimulating factor 1 day after mRNA injection.
Production and characterization of amplified tumor-derived cRNA libraries to be used as vaccines against metastatic melanomas
TLDR
The results show that unlimited amounts of cRNA representing tumor's transcriptome could be obtained and that this cRNA was a reliable source of a large variety of tumor antigens.
Induction of anti-tumor immunity with epidermal cells pulsed with tumor-derived RNA or intradermal administration of RNA.
TLDR
Effective anti-tumor immunity can be induced in mice utilizing RNA-pulsed epidermal cells for in vivo immunization or by injecting RNA intradermally into naïve mice.
Therapeutic cancer vaccines: at midway between immunology and pharmacology.
TLDR
This re-evaluation of the cancer vaccine landscape, suggests that future successful cancer immunotherapy will be combined immunotherapy, will be exquisitely schedule-dependent and will need new experimental models allowing for the exploration of the mechanisms of resistance and tumour escape, in the context of the physiology of the immune system of the elderly.
Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo
TLDR
The finding that RNA transcribed in vitro from cDNA cloned in a bacterial plasmid was highly effective in sensitizing DC shows that amplification of the antigenic content from a small number of tumor cells is feasible, thus expanding the potential use of RNA-pulsed DC- based vaccines for patients bearing very small, possibly microscopic, tumors.
Characterization of a messenger RNA polynucleotide vaccine vector.
We have constructed mRNA transcripts encoding luciferase and human carcinoembryonic antigen (CEA) which are capped, polyadenylated, and stabilized by human beta-globin 5' and 3' untranslated regions.…
Human peripheral blood monuclear cells transfected with messenger RNA stimulate antigen-specific cytotoxic T-lymphocytes in vitro
TLDR
It is shown here that fresh peripheral blood mononuclear cells (PBMCs) can be transfected with mRNA by electroporation, and are a convenient replacement of mRNA-transfected Mo-DCs for the in vitro monitoring of natural or vaccine-induced immune responses.
Human peripheral blood mononuclear cells transfected with messenger RNA stimulate antigen-specific cytotoxic T-lymphocytes in vitro.
TLDR
It is shown here that fresh peripheral blood mononuclear cells (PBMCs) can be transfected with mRNA by electroporation, and are a convenient replacement of mRNA-transfected Mo-DCs for the in vitro monitoring of natural or vaccine-induced immune responses.
Delivery of tumor-derived RNA for the induction of cytotoxic T-lymphocytes
TLDR
Electroporation was the most effective way yielding about 30% EGFP positive cells while less than 1% of DC expressed EGFP using the transferrin receptor transfection system, suggesting that this technology has the potential to induce cytotoxic T-cell response even when low level of antigen is delivered.
The Timing of GM-CSF Expression Plasmid Administration Influences the Th1/Th2 Response Induced by an HIV-1-Specific DNA Vaccine1
TLDR
The results suggest that the timing of cytokine expression determines the phenotype of the resultant Th response, and that DCs play important roles in the activation or modification of the Th2-type immune response induced by DNA vaccination.
...
...