Uses and methods for oncolytic virus targeting of IL-4/IL-13 and fusions thereof
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Publication Number
US-12404497-B2
Publication Date
2025-09-02
Expiration Date
Abstract
The present invention provides an oncolytic virus vector containing a sequence encoding IL-4 receptor targeted cargo protein, including IL-4 muteins and/or IL-13 muteins, the oncolytic virus encoded therefrom, the uses of the oncolytic virus for treating cancer.
Core Innovation
The invention relates to modified oncolytic virus vectors that carry an IL-4 receptor targeted cargo protein together with an IL-2 mutein, where the oncolytic virus vector is a modified adenovirus vector. The disclosed constructs are designed for delivery involving the tumor microenvironment and immunosuppressive cells, including tumor-associated macrophages and MDSCs.
The specification describes IL-4 receptor targeted cargo proteins as IL-4/IL-13 receptor targeted cargo proteins, including IL-4 muteins and IL-13 muteins. It further provides cytokine fusion and targeting concepts and embodiment definitions for IL-4/IL-13 muteins using explicit amino-acid sequence ranges and SEQ ID NO-defined embodiments.
The specification also discloses the IL-2 mutein included in the modified oncolytic virus vectors, with IL-2 mutein transgene options and defined amino-acid substitution patterns. It discusses signaling and functional rationale using signaling markers such as STAT5 phosphorylation, ERK1/ERK2, pERK, and PI3K signaling in connection with the disclosed mutein embodiments.
Claims Coverage
The document contains two independent claims. Across them, the main inventive features are a modified oncolytic adenovirus vector that encodes an IL-4 receptor targeted cargo protein and an IL-2 mutein, with an optional deletion of nucleotides encoding amino acids 122-129 of E1A polypeptide.
Il-4 receptor targeted cargo and il-2 mutein in modified oncolytic adenovirus
A modified oncolytic virus vector comprising at least one nucleic acid sequence encoding an IL-4 receptor targeted cargo protein and an IL-2 mutein, wherein the oncolytic virus vector is a modified adenovirus vector.
Modified adenovirus genome with optional e1a 122-129 deletion carrying il-4 receptor targeted cargo and il-2 mutein
A modified oncolytic adenovirus vector comprising an adenovirus genome, wherein optionally the nucleotides encoding amino acids 122-129 of E1A polypeptide are deleted, and at least one nucleic acid sequence encoding an IL-4 receptor targeted cargo protein and an IL-2 mutein.
Specific il-2 mutein substitution pattern and seQ id no-defined embodiments
An IL-2 mutein defined by amino-acid substitutions L80F, R81D, L85V, I86V, and I92F relative to wild-type human IL-2 with the sequence of SEQ ID NO:81, and at least one substitution selected from F42A, E62A, and Y45A relative to wild-type human IL-2 with the amino acid sequence of SEQ ID NO:81, and/or having an amino-acid sequence corresponding to any of SEQ ID NOs:82-109.
Il-4 receptor targeted cargo protein defined as il-4 mutein or il-13 mutein
The IL-4 receptor targeted cargo protein is an IL-4 mutein or an IL-13 mutein, and contains an amino-acid sequence corresponding to any of the amino-acid sequences of SEQ ID NOs:2-69.
Claim coverage centers on modified oncolytic adenovirus vectors that encode both an IL-4 receptor targeted cargo protein and an IL-2 mutein, with optional adenovirus E1A 122-129 deletion. The cargo and mutein are further limited by IL-4/IL-13 mutein identity and defined sequence or substitution patterns for the IL-2 mutein.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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