Methods and compositions for treating cancer with cancer-targeted adjuvants

Inventors

Hubbell, Jeffrey A. • Wilson, David S. • MARCHELL, Tiffany M. • GRAY, Laura T.

Assignees

University of Chicago

Abstract

Here, the inventors describe methods and compositions for targeting a TLR agonist to the tumor cell or stroma. Aspects of the disclosure relate to a polypeptide comprising a tumor targeting agent operatively linked to p(Man-TLR). Also disclosed are compositions and methods for treating cancer in a subject comprising administration of the polypeptide comprising the tumor targeting agent linked to p(Man-TLR) to the subject.

Core Innovation

The invention relates to cancer immunotherapy using a tumor-targeting polypeptide that covalently links a collagen binding domain to p(Man-TLR7). The collagen binding domain comprises the amino acid sequence of one of SEQ ID NOS: 1, 2, or 8, and the polypeptide targets a tumor in a subject and increases the accumulation of a TLR agonist in a tumor.

A core aspect is operatively linking the tumor/stroma-binding moiety to a TLR agonist copolymer that includes an APC mannose receptor-binding component connected to TLR agonist units, including TLR7 or TLR7/8 agonist units. The disclosure defines “operatively linked” as covalent or non-covalent linkage and includes targeting directed to tumor cells or to tumor stroma.

The disclosed approach is described as shifting the tumor microenvironment to an inflammatory state and supporting APC activation. The documented embodiments further include p(Man-TLR7)-based in situ cancer vaccine concepts with tumor-binding moieties, tumor-stroma binding moieties, collagen-binding serum albumin (CBD-SA) fusions, and combination with checkpoint blockade (PD-1 and/or CTLA4) to support cancer treatment.

Claims Coverage

Two independent claims are identified. Across them, the independent inventive features center on administering a collagen binding domain covalently linked to p(Man-TLR7), with sequence-defined collagen binding domains using SEQ ID NOS: 1, 2, or 8, and on cancer treatment, tumor targeting, increased tumor accumulation of a TLR agonist, and melanoma treatment.

Across the independent claims, the core coverage requires a polypeptide with a sequence-defined collagen binding domain (SEQ ID NOS: 1, 2, or 8) covalently linked to p(Man-TLR7). The claim scope is directed to cancer treatment, tumor targeting or increased tumor accumulation of the TLR agonist, and melanoma treatment.

Stated Advantages

Documented Applications