Previous estimates have linked roughly 10% of all cancers to viral infections, a percentage that is likely to increase as clinical associations between various cancers and putative onco-viruses are further strengthened1,2. We have discovered a novel human cytomegalovirus (HCMV) encoded protein in various aggressive solid tumors that is not present in healthy tissues.
1. Zapatka, M., Borozan, I., Brewer, D.S. et al. The landscape of viral associations in human cancers. Nat. Genet. 52, 320–330 (2020).
2. de Martel, C., Georges, D., Bray, F., Ferlay, J. & Clifford, G. M. Global burden of cancer attributable to infections in 2018: A worldwide incidence analysis. Lancet Glob. Health 8, 180-190 (2020).
One of the biggest problems in current targeted therapy for solid tumors is the lack of tumor-specific targets that are absent in vital organ systems. This results in undesirable, and at times fatal, side effects that arise from anti-tumor therapies unintentionally affecting healthy, nontumor tissues (on-target, off-tumor). The HCMV proteins that we have discovered in various solid tumors are only expressed in virus infected cancer/cancer-associated cells and therefore allow the use of aggressive, targeted approaches to eliminate the tumor without harming healthy, uninfected cells and tissues. HCMV employs a wide range of immunosuppressive mechanisms to evade the human immune system1; emerging research indicates that these same mechanisms may be linked to tumor immunosuppression2. Therefore, besides targeting the tumor, our ADCs could also potentially relieve immunosuppression within the tumor microenvironment and adjuvate targeted immunotherapy.
1. Griffiths, P. & Reeves, M. Pathogenesis of human cytomegalovirus in the immunecompromised host. Nat. Rev. Microbiol. 19, 759–773 (2021).
2. El Baba, R. & Herbein, G. Immune Landscape of CMV Infection in Cancer Patients: From "Canonical" Diseases Toward Virus-Elicited Oncomodulation. Front Immunol. 12, 1-17 (2021).
Viruses can mutate, resulting in different clinical strain variants circulating in the overall patient population. By systematically engineering therapeutic antibodies that display strong binding affinities to highly conserved epitopes across different HCMV strain variants, we are able to reach the full spectrum of virally infected cancer patients with the same therapy.
We are currently developing first-in-class antibody drug conjugates (ADCs) harboring next-generation linker technologies to target HCMV antigens in cancer. To learn more about our therapeutic candidates please visit our pipeline page.
