Method of manufacturing dual specific T-cells for use in cancer immunotherapy
Inventors
Assignees
Versiti Blood Research Institute Foundation Inc • Versiti Blood Research Foundation Inc
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Publication Number
US-11965177-B2
Publication Date
2024-04-23
Expiration Date
Abstract
The present invention relates to autologous dual-specific lymphocytes, methods of making and uses for the treatment of tumors. In particular, the invention relates to methods producing autologous dual-specific lymphocytes comprising an endogenous receptor for at least one tumor associated antigen and an exogenous receptor for a strong antigen
Core Innovation
The invention relates to autologous dual-specific lymphocytes for cancer immunotherapy in which a population of lymphocytes is isolated from a patient and each lymphocyte expresses an endogenous receptor for a tumor associated antigen (TAA). The lymphocytes are genetically engineered to express an additional receptor for a strong antigen, such that the resulting dual-specific lymphocytes target a plurality of TAAs and the strong antigen.
A strong antigen is provided to activate, expand, and recruit the dual-specific CD8 T cells and to overcome tumor immunosuppression in the tumor microenvironment. The treatment combines administration of the engineered dual-specific cells with injection of the strong antigen into or near the tumor to induce tumor regression and durable tumor regression and protection.
The disclosure further provides purified cell populations and compositions that include the engineered dual-specific lymphocytes with pharmaceutically acceptable carriers, together with production methods for isolating, purifying tumor-specific lymphocytes, and genetically engineering to express a second receptor for a strong antigen. Documented preclinical examples report enhanced tumor regression/eradication and long-term protective immunity, increased CD8 expansion/function/migration, reduced Tregs and MDSCs, and altered inhibitory receptor profiles.
Claims Coverage
The partial content includes two independent claims: clm-00001 and clm-00009. Together, they cover both an engineered purified population of autologous dual-specific lymphocytes and a method of producing such an autologous population, with inventive features directed to dual specificity for tumor-associated antigens and a strong antigen, plus autologous sourcing and genetic engineering.
Purified autologous dual-specific lymphocyte population targeting multiple TAAs and a strong antigen
A purified population of autologous dual-specific lymphocytes in which each lymphocyte expresses an endogenous receptor for a tumor associated antigen (TAA) and is genetically engineered to express an additional receptor for a strong antigen, wherein the population targets a plurality of TAAs and the strong antigen.
Producing an autologous dual-specific lymphocyte population by isolating, purifying tumor-specific lymphocytes, and engineering a second receptor to a strong antigen
A method of producing an autologous population of dual-specific lymphocytes that target a plurality of tumor associated antigens and at least one strong antigen, comprising isolating lymphocytes from a patient, purifying the tumor-specific lymphocytes, and genetically engineering the purified lymphocytes to express a second receptor specific to a strong antigen, wherein the resulting population comprises dual-specific lymphocytes.
The independent claims are directed to (i) a purified autologous dual-specific lymphocyte population defined by endogenous TAA specificity plus an engineered second receptor for a strong antigen, and (ii) a production process defined by isolating patient lymphocytes, purifying tumor-specific lymphocytes, and genetically engineering a second strong-antigen receptor to yield dual-specific lymphocytes.
Stated Advantages
Induce durable tumor regression and protection.
Enhanced tumor regression/eradication and long-term protective immunity.
Increase CD8 expansion/function/migration.
Reduce Tregs and MDSCs.
Alter inhibitory receptor profiles.
Documented Applications
Cancer immunotherapy using autologous dual-specific lymphocytes targeting tumor associated antigens (TAAs) together with providing a strong antigen to activate, expand, and recruit dual-specific CD8 T cells in or near the tumor.
Preclinical example testing using B16-F10 melanoma with recombinant Listeria (LM-OVA) reporting enhanced tumor regression/eradication and long-term immunity.
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