Using a validated anti-cancer treatment to eliminate or reduce HIV-infected cells
Around the world, 30 million people are infected with HIV. Preventing the development of AIDS in infected patients requires an expensive regimen of multiple antiretroviral medications per day. Chronic daily therapy is difficult to implement for certain patients and in some settings, and long-term antiviral therapy has side effects. Even with successful antiretroviral therapy HIV-infected cells remain and HIV rebounds immediately if antiviral therapy is discontinued. Dr. Wagner and colleagues are working on cellular therapy as a strategy that might control or eliminate HIV from the body. If successful, this might allow HIV-infected patients to discontinue daily antiviral medications.
The treatment is based on chimeric antigen receptor (CAR) T cells. T cells are an immune system component that attacks abnormal cells – for example, cells that are cancerous or virally infected. Interaction between receptors on the surface of T cells and molecules on aberrant cells activates a targeted immune response directed by T cells. CARs are T cell receptors engineered to have an extracellular domain based on an antibody that binds to cancer or viral marker, linked to an intracellular domain designed to activate the T cells, which leads to killing of cells with the marker. CAR T cell therapies for some cancers have shown a dramatic increase in patient survival, compared to standard chemotherapy. In some clinical trials CAR T cells persisted for years. These features suggest that CAR T cells have potential to be an effective long-term HIV treatment or cure.
Wagner’s group generated CAR T cells with broadly neutralizing monoclonal antibody domains that recognize multiple epitopes on HIV envelope proteins. Because T cells are themselves susceptible to HIV, the scientists used gene editing to eliminate expression of the CCR5 protein required for HIV infection. In vitro, these HIV-resistant anti-HIV CAR T kill HIV-infected cells and effectively control viral replication.
Wagner is currently funded by the National Institutes of Health to test the CAR T cells in vivo, using mouse and primate models of HIV. He is interested in partnerships to further develop and conduct clinical trials of cell-based therapies for infectious diseases, including HIV as well as other significant infections such as tuberculosis, and EBV-associated post-transplant lymphoproliferative disorder.
Stage of Development
- Pre-clinical in-vitro
- Preclinical in vivo
- Collaborative research opportunity
- Sponsored research agreement
- Consultation agreement
- Licensing agreement
- Hale M, Mesojednik T, Romano Ibarra GS, Sahni J, Bernard A, Sommer K, Scharenberg AM, Rawlings DJ, Wagner TA. Engineering HIV-Resistant, Anti-HIV Chimeric Antigen Receptor T Cells. Mol Ther. 2017;25(3):570-579. doi: 10.1016/j.ymthe.2016.12.023. Epub 2017 Jan 28. PMID:28143740
- Wagner TA. Combining Cell and Gene Therapy in an Effort to Eradicate HIV. AIDS Patient Care STDS. 2016 Dec;30(12):534-538. PMID: 27905840
- Wagner TA, McLaughlin S, Garg K, Cheung CY, Larsen BB, Styrchak S, Huang HC, Edlefsen PT, Mullins JI, Frenkel LM. HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection. Science. 2014 Aug 1;345(6196):570-3. doi: 10.1126/science.1256304. Epub 2014 Jul 10. PMID: 25011556
To learn more about partnering with Seattle Children’s Research Institute on this or other projects, please contact:
Dr. Elizabeth Aylward
Director, Office of Science-Industry Partnerships