Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma

mRNA technology has demonstrated potential for use as an effective cancer immunotherapy. However, inefficient in vivo mRNA delivery and the requirements for immune co-stimulation present major hurdles to achieving anti-tumour therapeutic efficacy. Therefore, we used a cationic hyper-branched cyclode...

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Bibliographic Details
Published in:Cancers 2023-07, Vol.15 (14), p.3748
Main Authors: Khazaei Monfared, Yousef, Mahmoudian, Mohammad, Zakeri-Milani, Parvin, Cecone, Claudio, Hayashi, Tomoya, Ishii, Ken J, Conde, João, Matencio, Adrián, Trotta, Francesco
Format: Article
Language:English
Subjects:
Adaptive immunity
Antigens
Cancer
Cancer immunotherapy
Cancer therapies
CD8 antigen
Cell culture
Cyclodextrin
Cyclodextrins
Cytotoxicity
Efficiency
Endosomes
Ethylenediaminetetraacetic acid
Health aspects
Immune system
Immunotherapy
Lymphocytes T
Malignancy
Melanoma
Messenger RNA
Metastases
Microscopy
mRNA
Nanoparticles
Plasma membranes
Polymer industry
Polymers
Proteins
Spleen
T cells
Transfection
Tumors
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Summary:mRNA technology has demonstrated potential for use as an effective cancer immunotherapy. However, inefficient in vivo mRNA delivery and the requirements for immune co-stimulation present major hurdles to achieving anti-tumour therapeutic efficacy. Therefore, we used a cationic hyper-branched cyclodextrin-based polymer to increase mRNA delivery in both in vitro and in vivo melanoma cancer. We found that the transfection efficacy of the mRNA-EGFP-loaded Ppoly system was significantly higher than that of lipofectamine and free mRNA in both 2D and 3D melanoma cancer cells; also, this delivery system did not show cytotoxicity. In addition, the biodistribution results revealed time-dependent and significantly higher mEGFP expression in complexes with Ppoly compared to free mRNA. We then checked the anti-tumour effect of intratumourally injected free mRNA-OVA, a foreign antigen, and loaded Ppoly; the results showed a considerable decrease in both tumour size and weight in the group treated with OVA-mRNA in loaded Ppoly compared to other formulations with an efficient adaptive immune response by dramatically increasing most leukocyte subtypes and OVA-specific CD8+ T cells in both the spleen and tumour tissues. Collectively, our findings suggest that the local delivery of cationic cyclodextrin-based polymer complexes containing foreign mRNA antigens might be a good and reliable concept for cancer immunotherapy.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15143748