How Genetically Modified T-Cells Attack Cancer

This patent describes how human T cells are genetically engineered to express a special receptor (CAR) that specifically targets and kills cancer cells, particularly those with the CD19 marker, offering a new way to treat cancer.

What it covers

This patent describes a pharmaceutical composition containing human T cells that have been genetically modified. These T cells are engineered to produce a special protein on their surface called a Chimeric Antigen Receptor (CAR). This CAR is designed with several key parts: a 'CD19 antigen binding domain' that acts like a hook to specifically grab onto CD19 proteins found on certain cancer cells, a 'transmembrane domain' that anchors the CAR to the T cell's surface, a '4-1BB costimulatory signaling region' that helps activate the T cell, and a 'CD3 zeta signaling domain' (specifically using the amino acid sequence of SEQ ID NO: 24) which is crucial for the T cell to launch its attack. When these modified T cells are given to a human with cancer, they are designed to find and destroy cancer cells expressing CD19. For example, a patient with a type of leukemia or lymphoma that has CD19-positive cancer cells could receive these specially prepared T cells to fight their disease.

What it doesn't cover

• —CAR T-cell therapies that target cancer cells expressing antigens other than CD19.
• —CAR T-cell therapies that use a costimulatory signaling region different from 4-1BB.
• —CAR T-cell therapies where the CD3 zeta signaling domain does not match the specific amino acid sequence of SEQ ID NO: 24.
• —T-cell therapies that are not genetically modified to express a Chimeric Antigen Receptor (CAR).
• —CAR T-cell therapies intended for uses other than treating cancer in a human.

The clever bit

The novelty lies in the specific combination of a CD19-targeting domain with both a 4-1BB costimulatory signal and a CD3 zeta signaling domain within a single CAR. This particular arrangement ensures that the engineered T cells not only recognize cancer cells but also receive the necessary 'go' signals to become fully activated, multiply, and persist in the body to effectively fight the tumor.

Why it matters

This patent is foundational to the development of Chimeric Antigen Receptor (CAR) T-cell therapy, a significant advancement in cancer treatment. It details the specific engineering of T cells to target CD19, a marker found on many blood cancers. This technology has led to the creation of 'living drugs' that can achieve deep and lasting remissions in patients with certain types of leukemia and lymphoma who previously had limited options.

Real-world examples

• 1.Kymriah (tisagenlecleucel) for certain leukemias and lymphomas
• 2.Yescarta (axicabtagene ciloleucel) for certain lymphomas
• 3.Tecartus (brexucabtagene autoleucel) for certain lymphomas
• 4.Breyanzi (lisocabtagene maraleucel) for certain lymphomas