Powerful CAR T Cell Therapy Against Aspergillosis

Introduction

This innovative CAR T cell therapy targets antigens associated with Aspergillus, a fungal pathogen known for causing severe infections, especially in immunocompromised patients. By engineering CAR T cells to recognize and attack Aspergillus-associated antigens, this therapy presents a powerful, targeted approach to combating a fungal threat that often proves resistant to conventional treatments. For companies in immunotherapy, infectious disease, and pharmaceuticals, this CAR T cell therapy offers a groundbreaking tool for expanding therapeutic options in fungal infection care, particularly for vulnerable populations in hospitals and clinical settings.

The Challenge: Treating Aspergillus Infections in At-Risk Patients

Aspergillus infections can lead to serious health complications and are a significant risk to patients with weakened immune systems, such as those undergoing chemotherapy, organ transplants, or chronic immunosuppressive therapies. These infections often resist traditional antifungal treatments, leaving patients with limited options and substantial health risks. Healthcare providers urgently need effective, targeted therapies that address Aspergillus infections without compromising the patient’s already weakened immune system.

Targeted CAR T Cell Therapy for Precise Infection Control

This CAR T cell therapy technology provides a precise solution by using CAR T cells engineered to identify and attack Aspergillus-associated antigens. This targeted approach allows for a powerful immune response against Aspergillus infections, delivering greater efficacy while preserving the integrity of the patient’s overall immune system. Patients benefit from a robust, immune-mediated defense specifically aimed at fungal cells, reducing the chances of infection progression and enabling faster recovery. With its precision and immune compatibility, this CAR T therapy represents a safer, more efficient alternative to traditional antifungal treatments.

Key Benefits for Pharmaceuticals and Infectious Disease Treatment

For pharmaceutical companies, this CAR T therapy technology represents a pivotal advancement in the treatment of fungal infections, opening the door to safer and more effective options for immunocompromised patients. Healthcare facilities and immunotherapy providers can leverage this technology to enhance infection management, offering a critical line of defense for at-risk patients. Its precision-targeted action aligns with the trend toward patient-specific treatments, supporting both individualized care and improved outcomes for vulnerable populations.

Invest in Advanced Fungal Infection Control

Licensing this CAR T cell therapy for Aspergillosis positions your company at the forefront of innovative immunotherapy solutions. By delivering a targeted, powerful response to deadly fungal infections, your business can offer hope to immunocompromised patients and lead the way in advanced infectious disease treatment. This technology is a valuable investment for companies focused on improving patient safety, expanding immunotherapy applications, and supporting groundbreaking treatments in infectious disease care.

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Abstract
Claims

Provided herein are compositions and methods for targeted treatment of Aspergillus-associated diseases and disorders in mammals, such as diseases and disorders associated with Aspergillus infection.

1. A chimeric antigen receptor (CAR) polypeptide, comprising an Aspergillus (ASP) antigen-binding domain that binds to an ASP antigen; a transmembrane domain; an intracellular signaling domain; and at least one co-stimulatory signaling region.

2–3. (canceled)

4. The CAR polypeptide of claim 1, wherein the ASP antigen is a galactofuranose-containing antigen, such as GalF4.

5. (canceled)

6. The CAR polypeptide of claim 1, wherein the ASP antigen-binding domain is an anti-galactofuranose scFv.

7. (canceled)

8. The CAR polypeptide of claim 1, wherein the transmembrane domain comprises the transmembrane domain of CD28 and/or 41BB.

9. The CAR polypeptide of claim 1, wherein the intracellular signaling domain comprises at least one signaling domain of any one of the polypeptides CD8, CD3ζ, CD3δ, CD3γ, CD3ε, CD32, DAP10, DAP12, CD79a, CD79b, CD28, CD3C, CD4, b2c, 41BB, ICOS, CD27, CD28δ, CD80, NKp30, OX40, FcγRI-γ, FcγRIII-γ, FcεRI-β, Fcε,RI-γ, mutants thereof, or any combinations thereof.

10. The CAR polypeptide of claim 1, wherein the at least one co-stimulatory signaling region comprises a signaling domain of any one of the polypeptides CD8, CD3ζ, CD3δ, CD3γ, CD3ε, CD32, DAP10, DAP12, CD79a, CD79b, CD28, CD3C, CD4, b2c, 41BB, ICOS, CD27, CD28δ, CD80, NKp30, OX40, FcγRI-γ, FcγRIII-γ, FcεRI-β, FcεRI-γ, mutants thereof, or any combinations thereof.

11. The CAR polypeptide of claim 1, wherein the at least one co-stimulatory signaling region comprises a signaling domain of CD28 or a mutant thereof.

12–15. (canceled)

16. The CAR polypeptide of claim 9, wherein at least one signaling domain of the intracellular signaling domain comprises a native CD3ζ, or a mutant thereof.

17–19. (canceled)

20. The CAR polypeptide of claim 1, further comprising a hinge sequence, wherein the hinge sequence is derived from a CD8a molecule or a CD28 molecule.

21. (canceled)

22. A nucleic acid encoding the CAR polypeptide of claim 1.

23. A vector comprising the nucleic acid of claim 22.

24–25. (canceled)

26. A cell expressing the CAR polypeptide of claim 1, wherein the cell is an αβT cell, γδT cell, a Natural Killer (NK) cell, a Natural Killer T (NKT) cell, a B cell, an innate lymphoid cell (ILC), a cytokine induced killer (CIK) cell, a cytotoxic T lymphocyte (CTL), a lymphokine activated killer (LAK) cell, or a regulatory T cell.

27–31. (canceled)

32. The cell of claim 26, wherein the cell is a viral antigen-sensitized CTL, such as an EBV-sensitized CTL.

33–34. (canceled)

35. The cell of claim 26, wherein the cell exhibits an anti-fungal effect when the antigen binding domain of the chimeric antigen receptor polypeptide binds to ASP.

36. The cell of claim 26, which is allogeneic to a human patient to which it is administered, or is autologous to a human patient to which it is administered.

37–39. (canceled)

40. A method of treating an ASP-associated disease or disorder in a mammal in need thereof, the method comprising administering to the mammal an effective amount of the CAR-expressing cells of claim 26, thereby effectively treating said disease or disorder in said mammal.

41. The method of claim 40, wherein the ASP-associated disease or disorder is pulmonary aspergillosis, allergic bronchopulmonary aspergillosis, aspergilloma, chronic pulmonary aspergilloma, severe asthma with Aspergillus sensitization, chronic cavitary pulmonary aspergillosis, or chronic fibrosing pulmonary aspergillosis.

42. The method of claim 40, wherein the CAR-expressing cells administered to the mammal are autologous to said mammal, or wherein the CAR-expressing cells administered to the mammal are allogeneic to said mammal.

43. (canceled)

44. The method of claim 40, wherein the mammal is human.

Title

Car t cells that target aspergillus-associated antigens

Inventor(s)

Blake Tolu Aftab

Assignee(s)

Atara Biotherapeutics Inc

Patent #

20230010255

Patent Date

January 12, 2023