SUMMARY OF INVENTION

Human papilloma virus (HPV) causes 90% of cervical cancer and 70% of oral cancers. Although vaccines exist for HPV, they have no efficacy against its viral oncogenic proteins E6 and E7. The proteins are also undruggable by small molecules and inaccessible to antibodies except when presented as peptide fragments in HLA complexes on cancer cells. MSK investigators have developed a TCR mimic monoclonal antibody against the p11-p19 fragment of HPV E7.

The lead bispecific T-cell engager (BiTE) flexibly links the single chain variable fragments (scF_vs) of a CD3-engaging antibody and an HPV E7:HLA complex-engaging 3F8 antibody. This format yields higher cytotoxicity for cells containing the oncogenic peptide:HLA complex than the 3F8 monoclonal antibody or bispecific antibody  in an IgG format. When tested against a cell line expressing the target, 3F8 BiTEs induced cytotoxic killing with concentrations as low as 10ng/uL of E7p11-p19 peptide. 

ADVANTAGES

• High affinity of 3F8 BiTE to ultra-low density HPV E7p11-p19 peptide.
• Increased flexibility of a BiTE, which allows for increased interaction between antigen complex and
• T-cells.
• Easier to manufacture over TCR-engineered cellular therapies, which could facilitate development of an off-the-shelf drug.
• Lower risk of cellular rejection and cytokine release syndrome as BiTE platform.

MARKET OPPORTUNITY

HPV E7 p11-19 has been observed in virtually all cervical cancers. T-cells engineered with patient-isolated TCRs specific against this peptide have induced tumor regression in 50% of HPV-associated cancers (Nagarsheth et al., 2021). In addition, HPV is responsible for 70% of all oral cancers in the US as well as 90% of cervical and anal, >60% of penile, and over 70% of vaginal and vulvar cancers worldwide (source: Cancer.gov).

PATENT INFORMATION

PCT application (PCT/US2023/010189) filed in Jan 2023.

PUBLICATIONS

Dao et al. (2022) A TCR mimic monoclonal antibody for the HPV-16 E7-epitope p11-19/HLA-A*02:01 complex. PLoS One 17(3):e0265534. (Pubmed link)

LEAD INVESTIGATOR

David Scheinberg, PhD, MD, Vincent Astor Chair; and Chairman, Center for Therapeutics Center; Deputy Director for Therapeutic Discovery, Sloan Kettering Institute, MSK

CONTACT INFORMATION

James Delorme, Ph.D.

Licensing Manager
E-mail: [email protected]