Human papillomavirus (HPV) has been linked to many cancers including cervix, uterine, anus, vulva, vagina, and penis. Although HPV vaccines exist to prevent HPV-associated cancers, there are still more than 5,000 deaths caused by HPV-associated cancers each year in the US and cervical cancer continues to be the second leading cause of cancer death in women ages 20 to 39. Engineered T cell receptor (TCR) therapy has been effective in some patients with HPV16 E6 expressing cancers, however, there continues to be a need for more therapies targeting HPV16 E6, when current treatment options fail.
NCI inventors have identified two nanobodies (F5 and G9) against MHC/E6 by phage display technologies from the lab’s multiple dromedary camel VHH single domain libraries. F5 and G9 could recognize the MHC/E6 complex more specifically over the control nanobodies. CAR T cells using the F5 nanobody as the binding domain showed specific killing of the target tumor cells in mouse models. These nanobodies could potentially treat cancers associated with the expression of HPV16 E6.
- These anti- HPV E6/E7 nanobodies have an advantage, due to their small size, to potentially bind to epitopes unavailable to more conventional antibodies or TCRs
- Therapeutic applications include the unconjugated antibodies and their use as a targeting moiety for CARs, TCRs, RITs, ADCs, immunocytokines and bispecific antibodies