IP Library › Granted Patent US 12,286,642
Granted Patent B2
US 12,286,642 · App. 17/415,147 · Granted Apr 29, 2025

Chimeric antigen receptors (CARS) that bind osteosarcoma and their use in medicine

Inventors: Else Marit Inderberg (Oslo, NO); Sébastian Wälchli (Oslo, NO); Øyvind S. Bruland (Oslo, NO)
Assignee: Oslo Universitetssykehus HF
C12N5/0636A61K39/4611A61K39/4631A61K39/4644A61P35/04C07K14/70517C07K14/70532C07K16/30C12N15/62A61K2039/86A61K2239/31A61K2239/55C07K2317/622C07K2317/73C07K2319/03C07K2319/33
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,286,642
App. No.
17/415,147
Granted
Apr 29, 2025
Kind
B2
Abstract

Chimeric antigen receptors (CARs) are provided. When the CARs herein are expressed on the surface of immune cells, such immune cells may be directed to osteosarcoma cells. In a murine intraperitoneal model, the tumor growth was significantly delayed for T cells expressing a CAR comprising a scFv from TP1 or TP3 antibodies. Immune cells expressing the CARs herein display therapeutic effect in the form of decreased tumor volume in a murine model simulating metastatic osteosarcoma. Combined with the finding that stem cells from healthy bone marrow were not significantly affected by T cells expressing any of the CARs, the CARs may be used for the treatment of osteosarcoma.

Claims (18)

1. A Chimeric Antigen Receptor (CAR) comprising an antigen binding domain, a CD8α hinge domain, a CD8α transmembrane domain and an intracellular signaling domain; wherein

the antigen binding domain comprises a TP1 scFV-fragment comprising SEQ ID NO: 1 and SEQ ID NO: 2 connected by a peptide linker, and

the intracellular signaling domain comprises a CD3ζ signaling domain and a 4-1BB costimulatory domain.

2. The CAR according to claim 1 , wherein the hinge domain is represented by SEQ ID NO: 5.

3. The CAR according to claim 1 , wherein the transmembrane domain is represented by SEQ ID NO: 6.

4. The CAR according to claim 1 , wherein the intracellular signaling domain consists of a CD3ζ signaling domain and a 4-1BB costimulatory domain.

5. The CAR according to claim 1 , wherein the hinge domain is represented by SEQ ID NO: 5, and the transmembrane domain is represented by SEQ ID NO: 6.

6. A nucleic acid encoding the CAR according to claim 1 .

7. An immune cell transduced with the nucleic acid according to claim 6 .

8. An immune cell expressing the CAR according to claim 1 .

9. A pharmaceutical composition comprising immune cells according to claim 7 , wherein the immune cells are T cells or NK cells, wherein the pharmaceutical composition is a sterile aqueous solution.

10. A method of treating osteosarcoma comprising administering to a subject in need thereof a pharmaceutical composition according to claim 9 , wherein the immune cells express the encoded CAR.

11. A method of treating metastatic osteosarcoma comprising administering to a subject in need thereof a pharmaceutical composition according to claim 9 , wherein the immune cells express the encoded CAR.

12. A method of treating micrometastatic osteosarcoma comprising administering to a subject in need thereof a pharmaceutical composition according to claim 9 , wherein the immune cells express the encoded CAR.

13. A method of treatment of metastatic osteosarcoma, comprising the steps:

a) transducing a population of NK cells and/or T cells with a nucleic acid as defined in claim 6 , wherein the transduced cells express the encoded CAR, and

b) intravenously administering a pharmaceutical composition comprising a pharmaceutically effective dose of the cells from step a) to a patient diagnosed with metastatic osteosarcoma.

14. A pharmaceutical composition comprising immune cells according to claim 8 , wherein the immune cells are T cells or NK cells, and wherein the pharmaceutical composition is a sterile aqueous solution.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 24, 2022
From: WÄLCHLI, SÉBASTIEN; BRULAND, ØYVIND; INDERBERG, ELSE MARIT
To: OSLO UNIVERSITETSSYKEHUS HF
Reel/Frame 059085/0722 →
Priority Claims (1)
NO 20181636 · Dec 20, 2018 · national
Continuity (1)
Related Publication 20220175897A1 · Jun 9, 2022
References Cited (30)
US 10767184B2 · Kochenderfer · 2020 [cited by examiner]
US 20190192573A1 · Bjornsdorff · 2019 [cited by examiner]
WO 2016016341A1 · 2016 [cited by applicant]
WO 2017118745A1 · 2017 [cited by applicant]
WO WO2017217525A1 · 2017 [cited by applicant]
WO 2018033630A1 · 2018 [cited by applicant]
WO WO2021260129A1 · 2021 [cited by applicant]
Bruland et al., Expression and Characteristics of a Novel Human Osteosarcoma-associated Cell Surface Antigen, Canc. Res. 48: 5302-5309, Sep. 15, 1988. [cited by examiner]
GenBank Database, Accession No. AJ131748, version 1, Mus musculus mRNA for immunoglobulin heavy chain variable region, clone TP-1, Retrieved from <URL:https://www.ncbi.nlm.nih.gov/nuccore/AJ131748.1> [retrieved on May 1… [cited by examiner]
GenBank Database, Accession No. AJ131747, version 1, Mus musculus mRNA for immunoglobulin light chain variable region, clone TP-1, Retrieved from <URL:https://www.ncbi.nlm.nih.gov/nuccore/AJ131747.1> [retrieved on May 1… [cited by examiner]
Song et al. In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137 (4-1BB). Cancer Res 2011;71:4617-4627 and supplementary material… [cited by examiner]
Wycislo et al., The Immunotherapy of Canine Osteosarcoma: A Historical and Systematic Review, J. Vet. Intern. Med. 2015;29:759-769. [cited by examiner]
DeRenzo et al. (2014). Genetically Modified T-Cell Therapy for Osteosarcoma. In: Kleinerman, M.D., E. (eds) Current Advances in Osteosarcoma. Adv. Exp. Med. Biol. vol 804:323-340. Springer, Cham. https://doi.org/10.1007… [cited by examiner]
Li et al., Current status and future challenges of CAR-T cell therapy for osteosarcoma, Frontiers Immunol. 14:1290762, doi.org/10.3389/fimmu.2023.1290762, 12 pages, Dec. 22, 2023. [cited by examiner]
Ahmed, N. et al.; “Human Epidermal Growth Factor Receptor 2 (HER2)—Specific Chimeric Antigen Receptor—Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma”; Journal of Clinical Oncology, vol. 33, Issue No. 15… [cited by applicant]
International Search Report and Written Opinion for International Application PCT/EP2019/086309; International Filing Date: Dec. 19, 2019; Date of Mailing: May 11, 2020; 16 pages. [cited by applicant]
Köksal, H. et al.; “Chimeric antigen receptor preparation from hybridoma to T-cell expression”; Antibody Therapeutics, vol. 2, Issue No. 2; 2019; pp. 56-63. [cited by applicant]
Köksal, H. et al.; “Treating osteosarcoma with CAR T cells”; Scandinavian Journal of Immunology, vol. 89; 2018; 8 pages; doi: 10.1111/sji.12741. [cited by applicant]
Lauvrak, S. et al.; “Functional characterisation of osteosarcoma cell lines and identification of mRNAs and miRNAs associated with aggressive cancer phenotypes”; British Journal of Cancer, vol. 109, Issue No. 8; 2013; p… [cited by applicant]
Long, A. et al.; “Reduction of MDSCs with All-trans Retinoic Acid Improves CAR Therapy Efficacy for Sarcomas”; Cancer Immunology Research, vol. 4, Issue No. 10; 2016; pp. 869-880. [cited by applicant]
Morgan, R. et al.; “Case Report of a Serious Adverse Event Following the Administration of T Cells Transduced With a Chimeric Antigen Receptor Recognizing ERBB2”; Molecular Therapy, vol. 18, Issue No. 4; 2010; pp. 843-8… [cited by applicant]
Mount, C., et al.; “Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M + diffuse midline gliomas”; Nature Medicine, vol. 24, Issue No. 5; 2018; pp. 572-579. [cited by applicant]
Olafsen, T. et al.; “Cloning and Sequencing of V Genes from Anti-Osteosarcoma Monoclonal Antibodies TP-1 and TP-3: Location of Lysine Residues and Implications for Radiolabeling”; Nuclear Medicine and Biology, vol. 22, … [cited by applicant]
Olafsen, T.; “AJ131747: Mus musculus mRNA for immunoglobulin light chain variable region, clone TP-1”; Available on internet [https://www.ebi.ac.uk/ena/data/view/AL131747&display=text], retrieved Apr. 16, 2020; 2 pages. [cited by applicant]
Quintarelli, C. et al.; “Choice of costimulatory domains and of cytokines determines CAR T-cell activity in neuroblastoma”; Oncoimmunology, vol. 7, Issue No. 6; 2018; 16 pages; doi: 10.1080/2162402X.2018.1433518. [cited by applicant]
Srivastava, S., et al.; “Chimeric Antigen Receptor T Cell Therapy: Challenges to Bench-to-Bedside Efficacy”; Journal of Immunology, vol. 200, Issue No. 2; pp. 459-468. [cited by applicant]
Olafsen et al., “Erratum”; Nuclear Medicine and Biology, vol. 26; 1999; p. 599. [cited by applicant]
Wälchli, S. et al.; “A practical approach to T-cell receptor cloning and expression”; PLoS One, vol. 6, Issue No. 11; 2011; 11 pages; doi: 10.1371/journal.pone.0027930. [cited by applicant]
Walseng et al.; “A TCR-based Chimeric Antigen Receptor”; Scientific Reports, vol. 7, Issue No. 1; 2017; 10 pages; doi: 10.1038/s41598-017-11126-y. [cited by applicant]
Search Report received Oct. 30, 2023, for Chinese application No. 201980092529.1 with English Translation. [cited by applicant]