CD22 is a protein receptor found on the surface of B cells, which are a component of the body’s immune system. This receptor is involved in regulating the complex functions of these immune cells to help maintain a balanced response. Because of its specific activities and presence on B cells, scientists have identified it as a target for developing medical treatments for certain health conditions, opening new avenues for therapeutic intervention.
The Role of B Cells and the CD22 Marker
The immune system’s adaptive branch relies on a type of white blood cell called the B cell. These cells are responsible for producing antibodies, which are proteins designed to identify and neutralize foreign invaders like bacteria and viruses. This process is fundamental to generating long-term immunological memory, allowing the body to mount a swift response to future encounters.
On the surface of these B cells is the CD22 marker, a receptor protein that appears as they mature. It belongs to a family of proteins known as Siglecs, which are involved in cell-to-cell interactions and signaling.
CD22 is distinguished by its ability to recognize and bind to certain sugar molecules, specifically α2,6-linked sialic acids, which are present on the surface of many cells. This interaction is directly tied to its regulatory functions for controlling B cell behavior.
CD22 in Immune System Regulation
In a healthy immune system, the CD22 protein acts as an inhibitory receptor, functioning as a “brake” on B cell activity. When a B cell is activated by a foreign substance, CD22 helps moderate this process to prevent it from becoming too aggressive. This regulation ensures that the immune response is proportional to the threat and does not cause unnecessary damage to the body’s own tissues.
The inhibitory function of CD22 is achieved through its interaction with other proteins inside the B cell. Upon binding to its specific sugar-based ligands, CD22 recruits enzymes, such as the phosphatase SHP-1, to the B cell receptor complex. These enzymes dampen the activation signals, raising the threshold required to trigger a full B cell response.
This system is important for maintaining self-tolerance, which is the immune system’s ability to recognize and not attack its own healthy cells. Since the ligands that CD22 binds to are common on the body’s own cells, this interaction helps to suppress the activation of B cells that might otherwise react to self-antigens, helping to prevent autoimmune diseases.
Targeting CD22 in B Cell Cancers
In certain cancers originating from B cells, such as B-cell acute lymphoblastic leukemia (B-ALL) and some forms of non-Hodgkin lymphoma, the malignant cells continue to express the CD22 marker. This characteristic makes CD22 a therapeutic target. Because its expression is largely restricted to the B-cell lineage, treatments designed to recognize CD22 can selectively attack cancerous B cells while minimizing harm to other cell types.
The effectiveness of targeting CD22 is enhanced by its biological behavior. When a molecule binds to the CD22 receptor, the receptor and its cargo are pulled inside the cell in a process called internalization. This mechanism provides an opportunity to deliver a toxic payload directly into the cancerous B cell.
An advantage of using CD22 as a target is that it is not found on hematopoietic stem cells. These stem cells, located in the bone marrow, are responsible for generating all new blood cells. By sparing these stem cells, CD22-targeted therapies help preserve the body’s ability to replenish its blood supply after treatment, reducing some long-term side effects.
Therapeutic Approaches Involving CD22
Medical science has developed several strategies to harness the CD22 marker for treating B-cell cancers. These therapies are designed to use the protein as a homing beacon to direct treatments specifically to malignant cells.
Antibody-Drug Conjugates (ADCs)
One approach is the use of antibody-drug conjugates (ADCs), often described as a “smart bomb” therapy. This technology links a monoclonal antibody, engineered to seek out and attach to the CD22 protein, with a cytotoxic drug. The antibody acts as a delivery vehicle, circulating through the body until it finds a B cell expressing CD22. After binding, the cancer cell internalizes the ADC, and the toxic payload is released inside, leading to the cell’s destruction. An example is Inotuzumab ozogamicin (Besponsa), which consists of an anti-CD22 antibody attached to calicheamicin and is approved for treating relapsed or refractory B-cell acute lymphoblastic leukemia.
CAR-T Cell Therapy
Another strategy is CAR-T cell therapy, a form of “living drug” treatment. In this process, a patient’s own T cells, another type of immune cell, are extracted from their blood. These T cells are then genetically engineered in a laboratory to produce a receptor on their surface known as a Chimeric Antigen Receptor, or CAR. This new receptor is specifically designed to recognize and bind to the CD22 protein on B cells. Once the engineered T cells are infused back into the patient, they multiply and hunt down cells that have the CD22 marker, activating the T cell to kill the cancer cell. This approach has shown promise for patients whose cancers have relapsed after other treatments.
Immunotoxins
Immunotoxins represent a concept similar to ADCs, but with a different kind of payload. Instead of being linked to a synthetic chemotherapy drug, the anti-CD22 antibody is attached to a potent toxin derived from natural sources, such as plants or bacteria. This fusion protein is designed to deliver the toxin directly to the cancerous B cells, leading to their death by inhibiting cellular processes like protein synthesis. Moxetumomab pasudotox (Lumoxiti) is an example of a CD22-directed immunotoxin that combines an anti-CD22 antibody with a form of a bacterial toxin. After the immunotoxin binds to CD22 and is internalized, the toxin is released and shuts down the cell’s ability to make proteins, causing cell death.