Sandhya Sharma1,2, Wingchi K Leung1, Helen E Heslop1. 1. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas. 2. Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine.
Abstract
PURPOSE OF REVIEW: Virus-associated malignancies are a global health burden, constituting 10-12% of cancers worldwide. As these tumors express foreign viral antigens that can elicit specific T cell responses, virus-directed immunotherapies are a promising treatment strategy. Specifically, adoptive cell transfer of virus-specific T cells (VSTs) has demonstrated the potential to eradicate cancers associated with certain viruses. RECENT FINDINGS: Initial studies in 1990s first showed that VSTs specific for the Epstein-Barr virus (EBVSTs) can induce complete remissions in patients with post-transplant lymphoproliferative disease. Since then, studies have validated the specificity and safety of VSTs in multiple lymphomas and solid malignancies. However, challenges remain to optimize this platform for widespread use, including enhancing potency and persistence, overcoming the immunosuppressive tumor microenvironment, and streamlining manufacturing processes that comply with regulatory requirements. SUMMARY: This review focuses on data from clinical trials evaluating VSTs directed against three viruses (EBV, HPV and MCPyV), as well as recent preclinical and clinical advances, and potential future directions.
PURPOSE OF REVIEW: Virus-associated malignancies are a global health burden, constituting 10-12% of cancers worldwide. As these tumors express foreign viral antigens that can elicit specific T cell responses, virus-directed immunotherapies are a promising treatment strategy. Specifically, adoptive cell transfer of virus-specific T cells (VSTs) has demonstrated the potential to eradicate cancers associated with certain viruses. RECENT FINDINGS: Initial studies in 1990s first showed that VSTs specific for the Epstein-Barr virus (EBVSTs) can induce complete remissions in patients with post-transplant lymphoproliferative disease. Since then, studies have validated the specificity and safety of VSTs in multiple lymphomas and solid malignancies. However, challenges remain to optimize this platform for widespread use, including enhancing potency and persistence, overcoming the immunosuppressive tumor microenvironment, and streamlining manufacturing processes that comply with regulatory requirements. SUMMARY: This review focuses on data from clinical trials evaluating VSTs directed against three viruses (EBV, HPV and MCPyV), as well as recent preclinical and clinical advances, and potential future directions.
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