CD70 is a protein found on the surface of immune cells, functioning as a signaling molecule. It helps regulate immune responses and is normally tightly controlled, appearing only when immune cells are activated to orchestrate the body’s reactions to threats.
The Biological Role of CD70
CD70 acts as a ligand, binding to its primary partner, the CD27 receptor, found on lymphocytes like T-cells and B-cells. This interaction provides a co-stimulatory signal important for activating T-cells, promoting their growth, survival, and development into long-lasting memory T-cells.
Beyond T-cells, the CD70-CD27 interaction also influences B-cell function. It contributes to the activation and differentiation of B-cells, which produce antibodies. The controlled expression of CD70 ensures immune responses are robust but do not become overactive, maintaining immune system balance.
CD70 in Disease Processes
While CD70 expression is carefully regulated in healthy tissues, many cancers exhibit abnormal expression of this protein on their cell surface. This has been observed in various malignancies, including renal cell carcinoma, non-Hodgkin lymphoma, some leukemias, and glioblastoma. The presence of CD70 on tumor cells can provide survival signals, promoting uncontrolled growth and inhibiting programmed cell death.
Furthermore, CD70 on cancer cells can influence the tumor microenvironment. This interaction can lead to T-cell exhaustion or apoptosis in lymphocytes, helping cancer evade the immune system. CD70’s role is also being explored in autoimmune diseases, where its inappropriate or prolonged expression could contribute to chronic immune activation and tissue damage.
Targeting CD70 in Therapy
CD70’s limited expression in most healthy adult tissues, combined with its widespread presence on various tumor cells, makes it an attractive target for cancer therapies. Strategies are being developed to specifically target CD70-expressing cancer cells while minimizing harm to healthy cells.
Antibody-Drug Conjugates (ADCs)
ADCs are engineered molecules where an antibody, which binds to CD70 on cancer cells, is linked to a potent chemotherapy drug. Once bound, the ADC is internalized, releasing the drug inside the tumor cell. This delivers a concentrated dose of chemotherapy directly to the tumor, reducing systemic side effects.
CAR-T Cell Therapy
In CAR-T cell therapy, a patient’s T-cells are genetically engineered with a “chimeric antigen receptor” (CAR) that recognizes CD70 on cancer cells. Re-infused into the patient, these CAR-T cells identify and destroy CD70-expressing tumor cells.
Monoclonal Antibodies
Monoclonal antibodies targeting CD70 can block the interaction between CD70 on cancer cells and its receptor, CD27, preventing survival signals or mitigating immune evasion. Some antibodies can also “flag” cancer cells for destruction by other immune cells or directly induce cancer cell death. Cusatuzumab (ARGX-110) is an anti-CD70 antibody currently in clinical trials for leukemia treatment.