Methods and compositions for targeting Treg cells
Inventors
ARLEN, Philip M. • Tsang, Kwong Y. • DAVID, Justin M. • FANTINI, Massimo
Assignees
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Publication Number
US-12037410-B2
Publication Date
2024-07-16
Expiration Date
Abstract
The antibody NEO-201 is shown to bind to Treg cells, and its use in targeting Treg cells is described. NEO-201 may be used for isolation, detection, or purification of active Treg cells and also to kill Treg cells. Therapeutic methods and combination therapies using NEO-201 optionally in combination with another agent are described.
Core Innovation
The document describes NEO-201 as a humanized IgG1 antibody that binds cancer-associated glycosylated variants of CEACAM5 and CEACAM6 and is used as a tool to target regulatory T (Treg) cells. It reports that NEO-201 binds Tregs despite CEACAM5/CEACAM6 being largely absent on Tregs, linking this binding to functional Treg targeting in the context of cancer.
The document states that NEO-201 enables isolation and purification of functional Tregs, including an increase in the percentage of active Tregs after NEO-201-based selection compared with standard kits. It further states that NEO-201 can kill opsonized Tregs via complement-dependent cytotoxicity (CDC).
For therapeutic use, the document proposes in vivo anti-cancer immunotherapy by ablating Tregs, optionally decreasing Treg infiltration and potentiating anti-cancer immune responses. It further describes combination approaches with cancer vaccines and immune checkpoint inhibitors including PD-1/PD-L1 and CTLA-4, and extends the utility to detection/staining and ex vivo/in vitro killing workflows.
Claims Coverage
The partial content provides one independent claim (clm-00001) covering treating a CEACAM5- and CEACAM6-negative cancer patient using an antibody defined by specific VH/VL CDR sequences, with effects on Tregs, anti-cancer immune responses, and cancer cell burden or growth/proliferation. Dependent claims refine the independent claim by adding specific antibody constraints and additional treatment-agent options.
Treating CEACAM5 and CEACAM6 negative cancer by administering specific VH/VL CDR antibody
A method of treating cancer comprising administering an antibody comprising a VH and VL polypeptide comprising the same CDR sequences respectively contained in SEQ ID NO: 28 and SEQ ID NO: 29 to a patient comprising a cancer which is CEACAM5 and CEACAM6 negative, wherein the method kills Treg cells or decreases Treg cell infiltration into the CEACAM5 and CEACAM6 negative cancer.
Potentiating anti-cancer immune responses through Treg killing or reduced infiltration
The method further includes potentiating anti-cancer immune responses against the CEACAM5 and CEACAM6 negative cancer by killing Treg cells in the patient or decreasing Treg cell infiltration into the CEACAM5 and CEACAM6 negative cancer.
Reducing cancer cells or growth/proliferation while treating CEACAM5 and CEACAM6 negative cancer
The method further includes reducing the number of CEACAM5 and CEACAM6 negative cancer cells or the growth or proliferation rate of the CEACAM5 and CEACAM6 negative cancer in the patient.
Determining CEACAM5 and CEACAM6 negativity and/or lack of specific binding prior to or at administration
The method further comprises, prior to or at the time of said administering, determining that the cancer is CEACAM5 and CEACAM6 negative and/or does not specifically bind to the antibody.
Using an antibody with specific SEQ ID based CDR sequence identity constraints
The method uses an antibody that comprises the same CDR sequences respectively contained in SEQ ID NO: 28 and SEQ ID NO: 29, including refinements based on sequence identity constraints relative to SEQ ID numbers or amino-acid ranges.
Optionally using conjugated forms of the antibody
The method includes that the antibody is conjugated to a cytotoxic moiety, a label, a radioactive moiety, or an affinity tag.
Applying the method to enumerated cancer categories with CEACAM5/CEACAM6 negativity
The method is applied to selecting cancer that is CEACAM5 and CEACAM6 negative from enumerated cancer categories including hematologic malignancies, lung cancers, melanoma, gastrointestinal malignancies, ovarian cancer, squamous cell carcinoma of the head and neck, hepatocellular carcinoma, breast cancer, pancreatic cancer, mesothelioma, metastatic renal cell carcinoma, and prostatic cancer.
Excluding particular cancer types from the treated set
The method includes treating a type of cancer that is not colon cancer, breast cancer, prostate cancer, or lymphoma.
Combining with a specified other anti-cancer or immune-checkpoint agent
The method further includes that an “other agent” can be selected from various classes of anticancer drugs, nucleoside/biochemical pathway inhibitors, or immune checkpoint inhibitors/antibodies including PD-1 inhibitor and CTLA-4 inhibitor options.
Across the independent claim and provided refinements, the core coverage centers on administering the specified NEO-201 antibody defined by VH/VL CDR sequences (SEQ ID NO: 28 and SEQ ID NO: 29) to CEACAM5/CEACAM6-negative cancers to kill Tregs or decrease Treg infiltration, thereby potentiating anti-cancer immune responses and reducing cancer cell number or growth/proliferation, with a prerequisite determination of CEACAM5/CEACAM6 negativity and/or lack of specific binding. Dependent claims further restrict or elaborate the antibody form and permit combination with specified therapeutic-agent categories.
Stated Advantages
Kills Treg cells or decreases Treg cell infiltration into CEACAM5 and CEACAM6 negative cancer.
Potentiates anti-cancer immune responses against CEACAM5 and CEACAM6 negative cancer.
Reduces the number of CEACAM5 and CEACAM6 negative cancer cells or reduces the growth or proliferation rate of the CEACAM5 and CEACAM6 negative cancer.
Enables isolation and purification of functional Tregs (increased percentage of active Tregs after NEO-201-based selection versus standard kits).
Can kill opsonized Tregs via complement-dependent cytotoxicity (CDC).
Optionally decreases Treg infiltration and potentiates anti-cancer immune responses in vivo.
Supports combination with cancer vaccines and immune checkpoint inhibitors including PD-1/PD-L1 and CTLA-4.
Provides utility for detection/staining and ex vivo/in vitro killing workflows.
Documented Applications
In vivo anti-cancer immunotherapy by ablating Tregs, including potentially decreasing Treg infiltration and potentiating anti-cancer immune responses.
Combination therapy for anti-cancer treatment with cancer vaccines and immune checkpoint inhibitors including PD-1/PD-L1 and CTLA-4.
Use as a tool for detection/staining.
Use in ex vivo/in vitro killing workflows.
Isolation and purification of functional Tregs using NEO-201-based selection.
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