Consensus sequence of the antigen telomerase and the use thereof in preventive and therapeutic vaccination
Inventors
Aurisicchio, Luigi • Conforti, Antonella
Assignees
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Publication Number
US-12622955-B2
Publication Date
2026-05-12
Expiration Date
Abstract
A consensus sequence of the antigen telomerase (ConTRt) can be generated and used in preventive and therapeutic vaccination. The consensus sequence of telomerase was generated by the fusion of two sequences, one belonging to human telomerase (hTERT) and the other to dog telomerase (dTERT), with the aim of developing an effective vaccine for the treatment of tumors expressing both human and dog telomerase, hence in both the human and veterinary sectors.
Core Innovation
The invention concerns a telomerase antigen consensus sequence (conTRT / conTRt) generated as an antigen telomerase comprising sequence SEQ ID NO:1, where the nucleotide sequence comprises SEQ ID NO:4 or a sequence having a sequence identity of at least 80% with respect to SEQ ID NO:4. The antigen telomerase consensus is combined with a nucleotide sequence encoding the profilin-like protein of Toxoplasma gondii comprising SEQ ID NO:31.
The described constructs further optionally include fusion/improved telomerase epitopes from human (hTERT) and dog (dTERT) telomerase, with optional inclusion of the immunostimulatory profilin-like protein from Toxoplasma gondii (PFTG). The telomerase antigen consensus sequence is reported as being more immunogenic and cross-reactive than chimeric CaHu and HuCa constructs in mouse studies after DNA electroporation with a conTRT-encoding construct.
In animal studies, the described conTRT approach produces a prophylactic antitumor effect in a colon carcinoma CT26 model expressing human telomerase. In dog studies, immune responses are reported against both dog and human telomerase and PFTG, and telomerase-specific IFNγ responses are detected by ELISpot following administration with a conTRT-encoding construct.
Claims Coverage
The independent claim covers a nucleotide sequence encoding an antigen telomerase consensus (SEQ ID NO:1) that includes a defined nucleotide segment (SEQ ID NO:4 or ≥80% identity) together with a nucleotide sequence encoding the Toxoplasma gondii profilin-like protein (SEQ ID NO:31).
Nucleotide sequence encoding telomerase antigen consensus with defined segment and profilin-like protein
A nucleotide sequence encoding an amino acid consensus sequence of the antigen telomerase comprising sequence SEQ ID NO:1, wherein the nucleotide sequence comprises the nucleotide sequence SEQ ID NO:4, or a sequence having a sequence identity of at least 80% with respect to SEQ ID NO:4, and a nucleotide sequence encoding the profilin-like protein of Toxoplasma Gondii, wherein the nucleotide sequence encoding the profilin-like protein of Toxoplasma Gondii comprises SEQ ID NO:31.
Coverage is focused on a nucleotide sequence that encodes a telomerase antigen consensus together with the Toxoplasma gondii profilin-like protein, with the claim language anchored by SEQ ID NO:1, SEQ ID NO:4 or ≥80% identity, and SEQ ID NO:31.
Stated Advantages
More immunogenic and cross-reactive than chimeric CaHu and HuCa constructs in mouse studies.
Produces a prophylactic antitumor effect in a colon carcinoma CT26 model expressing human telomerase.
Induces immune responses against both dog and human telomerase and PFTG in dog studies.
Detects telomerase-specific IFNγ responses measured by ELISpot.
Documented Applications
Prophylactic antitumor effect in a colon carcinoma (CT26) model expressing human telomerase.
Immune response assessment against dog and human telomerase and PFTG in healthy beagles.
Immune response assessment against dog and human telomerase and PFTG in dogs with lymphoma.
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