Loaded Dendritic Cells that Enhance Cellular Immunotherapy for Cancer
Patent Number: Pending
Executive Summary:
General Description:
One immunotherapy approach to treating cancer provides patients with a vaccine of their own dendritic cells loaded with tumor antigens. Those dendritic cells migrate to a lymph node where they simulate T cells to generate an immune response, allowing the cells to express the target antigen that results in tumor killing. Enhancing that migration of dendritic cells to the local lymph node is critical for efficacy of this treatment strategy. The inventors have discovered that loading those dendritic cells with sarcosine, a common metabolite, significantly improves migration to local lymph nodes compared to previous strategies. This sarcosine addition for treatment can be applied to other cells such as T-cells in an adoptive immunotherapy strategy. This intracellular sarcosine loading method also has the potential to enhance migration of T-cells and stem cells allowing this treatment to be applicable in other diseases.
Future Directions:
Strengths:
Weaknesses:
Publications:
Seyfizadeh N, Muthuswamy R, Mitchell DA, Nierkens S, Seyfizadeh N. Migration of dendritic cells to the lymph nodes and its enhancement to drive anti-tumor responses. Crit Rev Oncol Hematol. 2016 Nov;107:100-110. doi:10.1016/j.critrevonc.2016.09.002. Epub 2016 Sep 9. Review. PubMed PMID: 27823637.
Mitchell DA, Batich KA, Gunn MD, Huang MN, Sanchez-Perez L, Nair SK, Congdon KL, Reap EA, Archer GE, Desjardins A, Friedman AH, Friedman HS, Herndon JE 2nd, Coan A, McLendon RE, Reardon DA, Vredenburgh JJ, Bigner DD, Sampson JH. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature. 2015 Mar 19;519(7543):366-9. doi: 10.1038/nature14320. Epub 2015 Mar 11. PubMed PMID: 25762141; PubMed Central PMCID: PMC4510871.
Inventor Bios: Maryam Rahman, Duane Mitchell
https://ufhealth.org/maryam-rahman/background
https://neurosurgery.ufl.edu/faculty-staff/research-faculty/mitchell/
Executive Summary:
- Invention Type: Therapeutic (Vaccine)
- Patent Status: Application pending
- Patent Link: http://technologylicensing.research.ufl.edu/technologies/15810_loaded-dendritic-cells-that-enhance-cellular-immunotherapy-for-cancer
- Research Institute: University of Florida
- Disease Focus: Cancer
- Basis of Invention: Sarcosine, also known as N-methylglycine, is a metabolite of an amino acid found naturally in biological tissues. Sarcosine stimulates migration of the antigen-presenting dendritic cells, therefore stimulating of immune response
- How it works: Dendritic cells are isolated from patients, and loaded with tumor antigens. To increase their potency, these cells are also loaded with sarcosine. The vaccine containing sarcosine-loaded cells is administered to the patient, and sarcosine supports migration of the dendritic cells to the lymph nodes, increasing the potency of immunotherapy
- Lead Challenge Inventor: Maryam Rahman, Duane Mitchell
- Inventors: Maryam Rahman, Duane Mitchell, Rolando Lovaton, Hasan Azari
- Development Stage: Preliminary data
- Novelty:
- Dendritic cell stimulation by sarcosine
- Dendritic cell stimulation by sarcosine
- Clinical Applications:
- Adoptive immunotherapy
General Description:
One immunotherapy approach to treating cancer provides patients with a vaccine of their own dendritic cells loaded with tumor antigens. Those dendritic cells migrate to a lymph node where they simulate T cells to generate an immune response, allowing the cells to express the target antigen that results in tumor killing. Enhancing that migration of dendritic cells to the local lymph node is critical for efficacy of this treatment strategy. The inventors have discovered that loading those dendritic cells with sarcosine, a common metabolite, significantly improves migration to local lymph nodes compared to previous strategies. This sarcosine addition for treatment can be applied to other cells such as T-cells in an adoptive immunotherapy strategy. This intracellular sarcosine loading method also has the potential to enhance migration of T-cells and stem cells allowing this treatment to be applicable in other diseases.
Future Directions:
- Clinical trials
Strengths:
- Increases efficacy of dendritic cell vaccination, enhancing adoptive T cell transfer
- Creates robust immune response, potentially improving survival in patients with cancer
- Uses patients own dendritic cells, decreasing unwanted immune response
Weaknesses:
- Very limited information is available about the invention (unpublished)
Publications:
Seyfizadeh N, Muthuswamy R, Mitchell DA, Nierkens S, Seyfizadeh N. Migration of dendritic cells to the lymph nodes and its enhancement to drive anti-tumor responses. Crit Rev Oncol Hematol. 2016 Nov;107:100-110. doi:10.1016/j.critrevonc.2016.09.002. Epub 2016 Sep 9. Review. PubMed PMID: 27823637.
Mitchell DA, Batich KA, Gunn MD, Huang MN, Sanchez-Perez L, Nair SK, Congdon KL, Reap EA, Archer GE, Desjardins A, Friedman AH, Friedman HS, Herndon JE 2nd, Coan A, McLendon RE, Reardon DA, Vredenburgh JJ, Bigner DD, Sampson JH. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature. 2015 Mar 19;519(7543):366-9. doi: 10.1038/nature14320. Epub 2015 Mar 11. PubMed PMID: 25762141; PubMed Central PMCID: PMC4510871.
Inventor Bios: Maryam Rahman, Duane Mitchell
https://ufhealth.org/maryam-rahman/background
https://neurosurgery.ufl.edu/faculty-staff/research-faculty/mitchell/
