Sergei Kusmartsev

Antibodies Against Tumor-Specific Myeloid Cells Aid Diagnosis and Treatment of Various Cancers

These antibodies can diagnose cancer or improve cancer immunotherapy by targeting a population of tumor-specific myeloid cells that contribute to tumor progression. Within the tumor microenvironment, certain cell types can cause immunosuppression, which promotes tumor progression and worsens prognosis.1 Identifying these cell types can better inform cancer diagnosis, and targeting them can improve the immune response during cancer therapy. Cancer diagnosis often requires invasive medical procedures difficult for some patients, such as biopsies or endoscopies, and common diagnostic procedures lack precision to track tumor response or recurrence after treatment. Furthermore, while immunotherapy holds great promise for cancer treatment, the majority of patients do not respond to available immunotherapies, which often fail to overcome immunosuppression.

Researchers at the University of Florida have identified a subset of myeloid cells that express hyaluronidase to promote immunosuppression within the tumor microenvironment. An antibody targeting hyaluronidase-expressing cells can detect these tumor-specific cells and eliminate them for immunotherapy.

Application

Antibodies of hyaluronidase enzymes for diagnosis and treatment of cancer, including bladder, prostate, breast, brain, or lung cancers

Advantages

• Requires a blood sample only, allowing minimally invasive cancer diagnosis
• Monitors efficacy of other therapies, precisely tracking tumor response and recurrence
• Targets a cell population that causes immunosuppression within the tumor microenvironment, helping turn a “cold” tumor to “hot”
• Antibodies administer directly or inform development of CAR-T cells that also target Hyal2/Hyal1-expressing cells

Technology

Hyaluronan is a component of the extracellular matrix that undergoes degradation in the tumor microenvironment to promote tumor progression in bladder, prostate, breast, brain, and lung cancers. Tumor cells stimulate myeloid cells to express hyaluronidase (Hyal2/Hyal1), the enzyme responsible for hyaluronan fragmentation. These low-molecular weight hyaluronan fragments contribute to immunosuppression by upregulating PDL1 expression and stimulating cytokine release. Indeed, Hyal2/Hyal1-expressing myeloid cells are upregulated in bladder cancer patients. The monoclonal antibodies successfully target Hyal2/Hyal1-expressing myeloid cells in bladder cancer patients/models, and further research is evaluating their role in other solid cancers.