Combination therapy using a chimeric antigen receptor
Inventors
June, Carl H. • Watanabe, Keisuke • Guedan Carrio, Sonia • HEMMINKI, Akseli • Scholler, John • Young, Regina M.
Assignees
Novartis AG • Tilt Biotherapeutics Oy • University of Pennsylvania
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12653850-B2
Publication Date
2026-06-16
Expiration Date
Abstract
The invention provides compositions and methods for treating diseases such as cancer. The invention also relates to a method of administering a chimeric antigen receptor (CAR) therapy and an additional therapeutic agent, e.g., one or more cytokine molecules, e.g., a virus comprising a nucleic acid molecule encoding one or more cytokine molecules.
Core Innovation
The invention relates to treating a mesothelin expressing solid tumor in an immunocompetent human subject by administering mesothelin CAR-expressing T cells together with a chimeric serotype 5/3 oncolytic adenovirus. The oncolytic adenovirus comprises a nucleic acid molecule encoding TNFα and an IL-2 molecule, with nucleic acids defined by SEQ ID NO: 612 and 614 and a CAR comprising specified amino acid sequence options.
The CAR binds to mesothelin and optionally includes the signal peptide MALPVTALLLPLALLLHAARP (SEQ ID NO: 1). The mesothelin CAR-expressing cells target a cell of the mesothelin expressing solid tumor systemically and/or prevent the cell from egressing from the mesothelin expressing solid tumor.
The description content further recites a combination treatment framework in which the adenovirus is administered together with or in a defined relation to the mesothelin CAR-expressing cells, including embodiments where the adenovirus is administered about 1–5 days prior to or after administering the CAR-expressing cells. The provided example narrative indicates that combining mesothelin CAR T cells with cytokine-armed oncolytic adenovirus improves tumor lysis, T-cell activation and infiltration, tumor regression, and prevents metastasis in mouse pancreatic ductal adenocarcinoma models.
Claims Coverage
The relevant claim coverage centers on one independent claim directed to treating a mesothelin expressing solid tumor in an immunocompetent human subject using mesothelin CAR-expressing T cells together with a chimeric serotype 5/3 oncolytic adenovirus encoding TNFα and IL-2, with four additional inventive feature groups reflected in dependent claim refinements.
Combination therapy with mesothelin CAR-expressing T cells and serotype 5/3 oncolytic adenovirus
Administering a therapeutically effective amount of T cells that express a chimeric antigen receptor (CAR) molecule that binds to mesothelin and administering a chimeric serotype 5/3 oncolytic adenovirus comprising a nucleic acid molecule encoding a TNFα molecule and an IL-2 molecule.
Defined TNFα and IL-2 encoding nucleic acids and CAR sequence options
The nucleic acid molecule comprises the sequence of SEQ ID NO: 612 and 614, and the CAR comprises the amino acid sequence options identified by the listed SEQ ID NOs, optionally including the signal peptide MALPVTALLLPLALLLHAARP (SEQ ID NO: 1).
Systemic targeting and egress prevention
The mesothelin CAR-expressing cells target a cell of the mesothelin expressing solid tumor systemically and/or prevent the cell from egressing from the mesothelin expressing solid tumor.
Defined relative administration timing
The chimeric serotype 5/3 oncolytic adenovirus is administered about 1–5 days prior to or after administering the mesothelin CAR-expressing cells.
Defined first treatment interval dosing structure
In a first treatment interval, a single dose of therapeutically effective mesothelin CAR-expressing cells is administered together with a single dose of the chimeric serotype 5/3 oncolytic adenovirus.
The claim coverage is defined by the combination of mesothelin-binding CAR-expressing T cells with a chimeric serotype 5/3 oncolytic adenovirus encoding TNFα and IL-2, with specified SEQ ID NO: 612 and 614 nucleic acids, optional MALPVTALLLPLALLLHAARP inclusion, systemic targeting and/or egress prevention, and dependent refinements for timing and single-dose treatment interval structure.
Stated Advantages
Improved tumor lysis
Improved T-cell activation and infiltration
Tumor regression
Prevention of metastasis
Systemically targeting cells of the mesothelin expressing solid tumor.
Preventing a cell from egressing from the mesothelin expressing solid tumor.
Documented Applications
Treating a mesothelin expressing solid tumor in an immunocompetent human subject using mesothelin CAR-expressing T cells and a chimeric serotype 5/3 oncolytic adenovirus encoding TNFα and IL-2.
In mouse PDA models, combining mesothelin CAR T cells with cytokine-armed oncolytic adenovirus to improve tumor lysis, T-cell activation/infiltration, tumor regression, and prevent metastasis [procedural detail omitted for safety].
Treating mesothelioma, malignant pleural mesothelioma, pancreatic cancer, pancreatic ductal adenocarcinoma, or a metastatic solid tumor.
Interested in licensing this patent?