Cd22-specific T Cell Receptors and Adoptive T Cell Therapy for Treatment of B Cell Malignancies

Simple SummaryContent extracted from patent full text and abstract with AI.

This patent describes genetic constructs and methods for adoptive T cell therapy targeting B cell malignancies, specifically by creating T cell receptors (TCRs) that recognize and bind an epitope (a specific peptide) from the CD22 antigen when presented by the HLA-A*02 molecule. These engineered TCRs can be introduced into T cells, rendering them capable of locating and destroying B cell lymphoma or leukemia cells that express CD22, even if the antigen is not present on the cell surface. The invention includes nucleic acids encoding such TCRs, the TCR proteins, host cells (such as CD8+ T cells) expressing them, and pharmaceutical compositions for treatment purposes.

Use CasesContent extracted from patent full text and abstract with AI.

• Personalized cell-based immunotherapy for patients with B cell lymphomas or leukemias expressing CD22 and HLA-A*02 (such as diffuse large B-cell lymphoma, follicular lymphoma, B-cell ALL, etc.).
• Treatment of relapsed or refractory B cell malignancies where standard therapies (like chemotherapy, antibody therapy, or CAR-T therapy) have failed or are not suitable.
• Combination with other immunotherapies, such as monoclonal antibodies, CAR-T therapies targeting different antigens, or immune checkpoint inhibitors, to overcome tumor escape or resistance mechanisms.
• Potential use in cases where the tumor downregulates CD22 surface expression, as TCRs can target CD22-derived peptides presented intracellularly.
• Inclusion in pharmaceutical compositions or kits for clinical or research use targeting B cell malignancies.

BenefitsContent extracted from patent full text and abstract with AI.

• Enables targeting of intracellular antigenic epitopes, allowing destruction of cancer cells even when surface CD22 expression is lost, which is a limitation of antibody and CAR-based therapies.
• Expands eligibility for TCR-based therapy to the large proportion of the population carrying HLA-A*02, covering up to ~45% of Caucasians/West Europeans.
• Potentially greater specificity for malignant B cells, minimizing off-tumor toxicity by sparing cells that do not express the target peptide/HLA combination.
• Demonstrated efficacy in preclinical models for effective killing of various CD22+ B cell tumor lines and in vivo mouse models, including delayed tumor growth and increased survival.
• Customizable vectors and safety features (such as co-expressed 'safety tag' proteins like CD20) allow enhanced control and clinical safety, including the ability to ablate transferred cells if necessary.

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Inventors & Applicants

Patent Abstract

The present invention is directed to the field of immunotherapy, in particular, adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer, in particular, of B cell lymphoma or B cell leukemia. The invention provides a nucleic acid encoding at least one TCR alpha or beta chain construct of a TCR construct capable of specifically binding to a peptide of SEQ ID NO: 1, derived from the lineage specific antigen CD22, in the context of HLA-A2 and to subsequently lyse CD22-positive cells. The invention further provides a corresponding protein and host cell, e.g., a CD8+ T cell, pharmaceutical compositions comprising the same, and therapeutic use for treatment of B cell lymphoma or B cell leukemia, such as diffuse large B-cell lymphoma (DLBCL).