Methods of treatment using ex vivo expansion of cord blood t cells
Patent Number: US20130058909
Executive Summary:
General Description:
Umbilical cord blood transplantation uses blood collected from the umbilical cord after a baby is born. Unlike bone marrow, cord blood does not need to be perfectly matched to the patient’s tissues. Also, cord blood can be frozen and stored until needed. Ex vivo expansion of cord blood T cells was previously achieved with interleukin 2 (IL-2) and CD3/CD28 co-stimulatory beads. However, significant apoptosis was observed in T cells expanded in the presence of IL-2. This invention describes the cord blood T cell expansion in the presence of a different cytokine, IL-7. IL-7 not only reduces apoptosis of activated T lymphocytes and enhances their proliferation but also promotes functional maturation, leading to secretion of IFN-gamma and other key cytokines. The resulting T lymphocytes can be primed against lymphoid and myeloid leukemia cells to generate tumor-specific cytotoxic T cells. These findings offer a major step in fulfilling critical biological requirements to quickly generate a cellular product ex vivo, using a negligible fraction of a cord blood graft that provides a flexible adoptive immunotherapy platform for both children and adults.
Scientific Progress:
Autologous T cells reactive to acute myeloid leukemia cancer cells from patients were generated using a similar technique (ref. 1).
Quantitative lymphoid recovery in umbilical cord blood transplantation recipients was characterized in patients (ref. 2). is slower in the first 3 months, but these differences disappeared by 6 to 12 months after transplantation.
Future Directions:
Strengths:
Patent Status:
Publications:
Mehta RS, Chen X, Antony J, Boyiadzis M, Szabolcs P. Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts. J Immunother. 2016 Feb-Mar;39(2):71-80. doi: 10.1097/CJI.0000000000000107. PubMed PMID: 26849076; PubMed Central PMCID: PMC4746019.
Kanda J, Chiou LW, Szabolcs P, Sempowski GD, Rizzieri DA, Long GD, Sullivan KM, Gasparetto C, Chute JP, Morris A, McPherson J, Hale J, Livingston JA, Broadwater G, Niedzwiecki D, Chao NJ, Horwitz ME. Immune recovery in adult patients after myeloablative dual umbilical cord blood, matched sibling, and
matched unrelated donor hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012 Nov;18(11):1664-1676.e1. doi: 10.1016/j.bbmt.2012.06.005. Epub 2012 Jun 12. PubMed PMID: 22698485; PubMed Central PMCID: PMC3472115.
Inventor Bio: Paul Szabolcs
http://www.chp.edu/our-services/rare-disease-therapy/doctors-and-staff/paul-szabolcs
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Granted
- Patent Link: https://patents.google.com/patent/US20130058909/
- Research Institute: Duke University
- Disease Focus: Lymphoid and myeloid leukemia; infectious diseases
- Basis of Invention: T lymphocytes isolated from cord blood are expanded in cell culture. The expanded cells can be injected to the patient bloodstream directly or after exposure to cancer antigens
- How it works: T lymphocytes are isolated from the cord blood and exposed to interleukins and antibodies against CD3 and CD28 in cell culture. Cord blood T cells expanded according to the proposed method lack reactivity to the patient’s cells, but can be used to generate tumor-specific cytotoxic T cells
- Lead Challenge Inventor: Paul Szabolcs
- Development Stage: in vitro data
- Novelty:
- T cells are expanded in the presence of IL-7 and antibodies against CD3 and CD28 receptors
- Clinical Applications:
- Treatment of leukemia
- Treatment of viral infections
- Restoration of patient immune system after bone marrow ablation
General Description:
Umbilical cord blood transplantation uses blood collected from the umbilical cord after a baby is born. Unlike bone marrow, cord blood does not need to be perfectly matched to the patient’s tissues. Also, cord blood can be frozen and stored until needed. Ex vivo expansion of cord blood T cells was previously achieved with interleukin 2 (IL-2) and CD3/CD28 co-stimulatory beads. However, significant apoptosis was observed in T cells expanded in the presence of IL-2. This invention describes the cord blood T cell expansion in the presence of a different cytokine, IL-7. IL-7 not only reduces apoptosis of activated T lymphocytes and enhances their proliferation but also promotes functional maturation, leading to secretion of IFN-gamma and other key cytokines. The resulting T lymphocytes can be primed against lymphoid and myeloid leukemia cells to generate tumor-specific cytotoxic T cells. These findings offer a major step in fulfilling critical biological requirements to quickly generate a cellular product ex vivo, using a negligible fraction of a cord blood graft that provides a flexible adoptive immunotherapy platform for both children and adults.
Scientific Progress:
Autologous T cells reactive to acute myeloid leukemia cancer cells from patients were generated using a similar technique (ref. 1).
Quantitative lymphoid recovery in umbilical cord blood transplantation recipients was characterized in patients (ref. 2). is slower in the first 3 months, but these differences disappeared by 6 to 12 months after transplantation.
Future Directions:
- Pre-clinical studies on the efficacy of cancer treatment using the proposed technique
Strengths:
- Promotes development of cancer immunotherapy
Patent Status:
- Priority date: 2010-05-17
- Filing date: 2011-05-17
- Patent Grant: 2013-03-07
Publications:
Mehta RS, Chen X, Antony J, Boyiadzis M, Szabolcs P. Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts. J Immunother. 2016 Feb-Mar;39(2):71-80. doi: 10.1097/CJI.0000000000000107. PubMed PMID: 26849076; PubMed Central PMCID: PMC4746019.
Kanda J, Chiou LW, Szabolcs P, Sempowski GD, Rizzieri DA, Long GD, Sullivan KM, Gasparetto C, Chute JP, Morris A, McPherson J, Hale J, Livingston JA, Broadwater G, Niedzwiecki D, Chao NJ, Horwitz ME. Immune recovery in adult patients after myeloablative dual umbilical cord blood, matched sibling, and
matched unrelated donor hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012 Nov;18(11):1664-1676.e1. doi: 10.1016/j.bbmt.2012.06.005. Epub 2012 Jun 12. PubMed PMID: 22698485; PubMed Central PMCID: PMC3472115.
Inventor Bio: Paul Szabolcs
http://www.chp.edu/our-services/rare-disease-therapy/doctors-and-staff/paul-szabolcs