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Teleost invariant chain cancer vaccine

A constant chain, true bone technology, applied in vaccines, multivalent vaccines, DNA/RNA vaccination, etc., can solve problems such as the maximum insert size limit

Pending Publication Date: 2021-06-11
NOUSCOM AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

To optimize the probability of success, vaccines should target as many neoantigens as possible, however the maximum insert size of the vector is limited

Method used

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  • Teleost invariant chain cancer vaccine
  • Teleost invariant chain cancer vaccine
  • Teleost invariant chain cancer vaccine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0078] In the following, different aspects of the invention will be defined in more detail. Each aspect so defined may be combined with any other aspect unless expressly indicated to the contrary. In particular, any feature indicated as preferred or advantageous may be combined with any other feature indicated as preferred or advantageous.

[0079] In a first aspect of the invention, the invention relates to a polypeptide comprising:

[0080] (a) A fragment of the invariant chain of teleost (INV) comprising or consisting of 16 to 27 contiguous amino acids of the membrane proximal domain (MPD) of teleost INV, wherein the fragment has an enhanced T cell response subactivity and MPD is characterized by an amino acid sequence selected from the group consisting of:

[0081] (i) NQRX 1 DIKSLEEQX 2 SX 3 LX 4 x 5 x 6 x 7 TX 8 GRSX 9 x 10 (SEQ ID NO:001)

[0082] in

[0083] x 1 for G or N, X 2 for H or N, X 3 for G or N, X 4 N or Q, X 5 for E or A, X 6 for Q or E, ...

Embodiment

[0144] Teleost invariant chains and their fragments convert non-immunogenic cancer antigens to immunogenic antigens

[0145] The immunogenicity of simian adenoviral vectors encoding five cancer neoantigens (Table 1, SEQ ID NO: 16 to SEQ ID NO: 20) derived from the CT26 mouse tumor cell line was evaluated in BalBC inbred mice . The vector GAd-penta encoding only five cancer neoantigens (penta) linked end-to-end plus an initial Met and a C-terminal HA tag (SEQ ID NO: 21) was found to be non-immunogenic unless the full-length teleost invariant chain sequence (BP_INV FL[SEQ ID NO:9] or PO_INV FL[SEQ ID NO:2]) or fragment thereof (fragment BP_FRAG_A[SEQ ID NO:10] or BP_FRAG_B[SEQ ID NO:11] or PO_FRAG_A[SEQ ID NO: 3] or PO_FRAG_B [SEQ ID NO: 4]) was added to the N-terminus of the penta antigen (SEQ ID NO: 22 to SEQ ID NO: 27). to 10 8 Mice were immunized with a single intramuscular immunization of a viral particle (vp) dose of GAd. Splenocytes were harvested two weeks after immu...

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Abstract

The present invention relates to polypeptides comprising a fragment of a teleost invariant chain optionally fused to one or more antigens or a teleost invariant chain fused to one or more antigens or antigenic fragments thereof, a polynucleotide encoding such polypeptides, vectors comprising such polynucleotides, collection of vectors comprising such polynucleotides and use of such polypeptides, polynucleotides, vectors for treating or preventing diseases, in particular tumor diseases. The teleost invariant chain polypeptides or fragments thereof act as "T cell enhancer" converting non-immunogenic antigenic sequences into immunogenic T cell antigens.

Description

[0001] The present invention relates to polypeptides, polynucleotides encoding such polypeptides, vectors comprising such polynucleotides, collections of vectors comprising such polynucleotides and the use of such polypeptides, polynucleotides, vectors for the treatment or prevention of hyperplastic Disease, preferably cancer, viral disease, fungal disease or bacterial disease, said polypeptide comprises a teleost constant chain fragment optionally fused with one or more than one antigen or with one or more than A teleost constant chain fused to an antigen or an antigen fragment thereof. Teleost constant chain polypeptides or fragments thereof serve as "T cell enhancers" that convert non-immunogenic antigenic sequences into immunogenic T cell antigens. [0002] Background of the invention [0003] Sometimes vaccines elicit suboptimal or no T cell immune responses. This poor induction of T cell immune responses is more common in the context of vaccination against antigens that ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/385A61K39/00A61P35/00
CPCA61K39/0011A61K39/385A61K2039/5256A61K2039/53A61K2039/605A61K2039/70C12N2710/10043C07K14/461A61P35/00C07K2319/03C12N2710/10343A61K39/464401A61K39/464414A61K39/001114
Inventor 阿尔弗雷多·尼科西亚埃莉萨·斯卡尔塞利阿明·拉姆
Owner NOUSCOM AG