Method to treat cancer with engineered T-cells
Inventors
Dropulic , Boro • Orentas, Rimas J. • Schneider, Dina • Krueger, Winfried
Assignees
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Publication Number
US-12193995-B2
Publication Date
2025-01-14
Expiration Date
Abstract
Novel adoptive immunotherapy compositions comprising co-cultured lentiviral vector-transduced autologous antigen presentation cells and T cells are provided herein as well as are methods of use of same in a patient-specific combination immunotherapy that can be used to treat cancers and other diseases and conditions.
Core Innovation
The invention relates to an adoptive immunotherapy composition that includes an autologous T-cell population transduced with one or more lentiviral vectors encoding single or multiple CARs. The CARs comprise isolated nucleic acid sequences selected from SEQ ID NO: 13, SEQ ID NO: 17, and SEQ ID NO: 19, and the transduced autologous T cells are co-cultured with autologous antigen presentation cells that are transduced with one or more lentiviral vectors expressing patient-derived tumor antigens.
The co-culture generates an active patient-specific autologous anti-tumor T-cell population capable of promoting in vivo expansion and persistence of patient-specific anti-tumor T-cells. This patient-specific activity results in tumor stabilization, tumor reduction, remission of cancer, or elimination of cancer in a patient-specific manner.
The disclosure further supports embodiments in which autologous antigen presentation cells include dendritic cells, and the dendritic cells can be autologous dendritic cells differentiated from monocytes. Additional embodiments include transducing the T cells with tumor-specific TCRs in addition to expressing CARs, and preselecting the T cells based on expression of activation- or memory-associated surface markers.
Claims Coverage
The provided claims cover an autologous, CAR-transduced T-cell population with a defined CAR payload, combined with co-culture of autologous lentivirally transduced antigen presentation cells expressing patient-derived tumor antigens, to generate an active patient-specific anti-tumor T-cell population that promotes in vivo expansion and persistence and can lead to tumor stabilization, tumor reduction, remission, or elimination. The claims also recite six additional inventive features.
CAR-transduced autologous T cells with defined lentiviral CAR sequences
An autologous T-cell population transduced with one or more lentiviral vectors encoding single or multiple chimeric antigen receptors (CARs), wherein the CARs comprise an isolated nucleic acid sequence selected from SEQ ID NO: 13, SEQ ID NO: 17, and SEQ ID NO: 19.
Co-culture with autologous lentivirally transduced antigen presentation cells expressing patient-derived tumor antigens
The transduced T cells are co-cultured with autologous antigen presentation cells transduced with one or more lentiviral vectors expressing patient-derived tumor antigens.
Active patient-specific anti-tumor T-cell population promoting in vivo expansion and persistence
Generating an active patient-specific autologous anti-tumor T-cell population capable of promoting in vivo expansion and persistence of patient-specific anti-tumor T-cells resulting in tumor stabilization, tumor reduction, remission of cancer, or elimination of cancer in a patient-specific manner.
Addition of tumor-specific TCRs
The T-cell population is additionally transduced with one or more lentiviral vectors that encode tumor-specific T-cell receptors (TCRs).
Monocyte-derived autologous dendritic cells as antigen presentation cells
The autologous antigen presentation cells are autologous dendritic cells differentiated from monocytes.
T-cell preselection based on activation or memory-associated surface markers
The T cells are preselected based on expression of specific activation or memory-associated surface markers.
The claim coverage is centered on patient-specific adoptive immunotherapy using CAR-transduced autologous T cells and autologous lentivirally transduced antigen presentation cells expressing patient-derived tumor antigens. Dependent features further specify tumor-specific TCRs, monocyte-derived autologous dendritic cells, and T-cell preselection based on activation- or memory-associated surface markers.
Stated Advantages
Promotes in vivo expansion and persistence of patient-specific anti-tumor T-cells.
Leads to tumor stabilization.
Leads to tumor reduction.
Leads to remission of cancer.
Leads to elimination of cancer in a patient-specific manner.
Documented Applications
Treatment or management of patient-specific cancer via an adoptive immunotherapy composition for hematological cancers including leukemia, lymphoma, and multiple myeloma.
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