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Novel adjuvant class for use in immunotherapy and vaccination.

Reference Number TO 03-00207a

Challenge

Strong T cell responses are critical for obtaining effective protection in vaccination and immunotherapy. In particular novel therapeutic approaches addressing the T cell response have been shown to be essential for sophisticated vaccine design strategies. Protection to infection depends on the generation of a high number of memory T cells.  

IL-2 secretion and TCR expression of EBV-reactive T cells is greatly enhanced after 24h treatment with CD3kappa:


CD8 T cells have been retrovirally transduced with a low affinity, EBV-reactive TCR and tested with the antigenic peptide. Titration shows that lower amounts of the antigen are detected after CD3k treatment by the T cells. Both, specific cytokine release and TCR expression are increased by several folds after stimulation and CD3k effect. CP: control peptide (scrambled with the same AA composition).
IL-2 secretion and TCR expression of EBV-reactive T cells is greatly enhanced after 24h treatment with CD3kappa: CD8 T cells have been retrovirally transduced with a low affinity, EBV-reactive TCR and tested with the antigenic peptide. Titration shows that lower amounts of the antigen are detected after CD3k treatment by the T cells. Both, specific cytokine release and TCR expression are increased by several folds after stimulation and CD3k effect. CP: control peptide (scrambled with the same AA composition).

Technology

CD3kappa is a novel soluble splice variant of CD3delta that stabilizes T cell receptors (TCR) on the cell surface and greatly enhances antigen-dependent T cell functions and antigen sensitivity. 48 h treatment of PBMC with the peptide in vitro increases TCR expression up to 25-fold. In PBMC from immune suppressed patients, TCR expression is restored back to normal levels under CD3kappa treatment. Importantly, the sensitivity of T cells to antigen and the secretion of cytokines are increased by several logs even to very low doses of antigen (tested with various viral and bacterial antigens). The generation of memory T cell phenotype is also greatly enhanced after CD3k treatment. 

Enhancing TCR expression in T lymphocytes strongly increases immune responses. As many approaches in immunotherapy or vaccination aim to strengthen reactivity of the endogenous immune system, the peptide can be considered an interesting and completely new class of adjuvant candidate boosting also antigen-specific memory T cell generation. CD3kappa can easily be synthesized with solid phase peptide synthesizers and is therefore perfectly suited for in vivo applications, escaping the tremendous regulations which must be fulfilled with recombinant pharmaceuticals.

Commercial Opportunity

Exclusive in-licencing opportunity for clinical drug development.

Patent Situation

European patent application (EP 2032 601) is pending.

US patent application (US 12/306,176) is pending.