mRNA-Based Anti-TCR CDR3 Tumour Vaccine for T-Cell Lymphoma

Details

Serval ID
serval:BIB_7FA442B84D6D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
mRNA-Based Anti-TCR CDR3 Tumour Vaccine for T-Cell Lymphoma
Journal
Pharmaceutics
Author(s)
Tusup Marina, Läuchli Severin, Jarzebska Natalia Teresa, French Lars E., Chang Yun-Tsan, Vonow-Eisenring Maya, Su Andreas, Kündig Thomas M., Guenova Emmanuella (co-last), Pascolo Steve
ISSN
1999-4923
Publication state
Published
Issued date
07/07/2021
Volume
13
Number
7
Pages
1040
Language
english
Abstract
Efficient vaccination can be achieved by injections of in vitro transcribed mRNA (ivt mRNA) coding for antigens. This vaccine format is particularly versatile and allows the production of individualised vaccines conferring, T-cell immunity against specific cancer mutations. The CDR3 hypervariable regions of immune receptors (T-cell receptor, TCR or B-cell receptor, BCR) in the context of T- or B-cell leukaemia or lymphoma are targetable and specific sequences, similar to cancer mutations. We evaluated the functionality of an mRNA-based vaccine designed to trigger immunity against TCR CDR3 regions in an EL4 T-lymphoma cell line-derived murine in vivo model. Vaccination against the hypervariable TCR regions proved to be a feasible approach and allowed for protection against T-lymphoma, even though immune escape in terms of TCR downregulation paralleled the therapeutic effect. However, analysis of human cutaneous T-cell lymphoma samples indicated that, as is the case in B-lymphomas, the clonotypic receptor may be a driver mutation and is not downregulated upon treatment. Thus, vaccination against TCR CDR3 regions using customised ivt mRNA is a promising immunotherapy method to be explored for the treatment of patients with T-cell lymphomas.
Keywords
Pharmaceutical Science
Web of science
Open Access
Yes
Create date
30/07/2021 17:10
Last modification date
14/08/2021 6:36
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