HPV proteins, antibodies, and uses in managing abnormal epithelial cell growth
This disclosure relates to HPV proteins, antibodies, and uses in managing abnormal epithelial cell growth. In certain embodiments, this disclosure relates to detecting an HPV protein in a sample and correlating the presence as an indication that a subject is at risk of developing an HPV-related disease or condition. In certain embodiments, the HPV protein is E2 and/or E6. In certain embodiments, this disclosure relates to vaccinating or treating a subject for an HPV infection or related condition optionally in combination with immune-checkpoint inhibitors. In certain embodiments, this disclosure relates to HPV protein specific antibodies and binding agents for uses reported herein.
1. A chimeric antibody that specifically binds HPV16 E2 protein wherein the antibody comprises a light chain and a heavy chain,
wherein the light chain CDR1 is GYTFTSYP (SEQ ID NO: 67), CDR2 is INTNNGNP (SEQ ID NO: 68), and CDR3 is ARAGFEIYGDAFTYYGMDV (SEQ ID NO: 69); and
wherein the heavy chain CDR1 is TGDIGAYKF (SEQ ID NO: 72), CDR2 is EVSN (SEQ ID NO: 73), and CDR3 is SSYRGNTTL (SEQ ID NO: 74).
2. The chimeric antibody of claim 1 , wherein the light chain comprises the amino acid sequence of
(SEQ ID NO: 71)
MAWALLLLTLLTQGTGSWAQSALTQPASVSGSPGQLITISCIGSTGDIG
AYKFVSWYQQYPGKAPKLMIYEVSNRPSGISSRFSGSKSGNTASLTISG
LQVDDEADYYCSSYRGNTTLFGGGTKLTVLG.
3. The chimeric antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of
(SEQ ID NO: 66)
MDWTWRILFLVAAATGVHSQMQLEQSGSELKKPGASVKVSCKASGYTFT
SYPMNWVRQAPGQGLEWMGWINTNNGNPTYARDFTGRFVFSLDASVNTA
HLQITSLEAEDTAVYYCARAGFEIYGDAFTYYGMDVWGQGTTVTVSS.
4. The chimeric antibody of claim 1 , wherein the heavy chain comprises one or more of the following Fc mutations G236A, S239D, A330L, I332E, S267E, L328F, P238D, H268F, S324T, S228P, G236R, L328R, L234A, L235A, M252Y, S254T, T256E, M428L, and N434S
wherein the Fc mutations are in reference to following amino acid sequence starting at amino acid 119:
(SEQ ID NO: 179)
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVE
PKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWL
NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV
SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG.
5. A chimeric antibody that specifically binds HPV16 E2 protein wherein the antibody comprises a light chain and a heavy chain,
wherein the light chain CDR1 is SGRTTFA (SEQ ID NO: 62), CDR2 is IYNDGSH (SEQ ID NO: 63), and CDR3 is QTWGSGSVM (SEQ ID NO: 64); and
wherein the heavy chain CDR1 is GFTFTNYA (SEQ ID NO: 57), CDR2 is ITDNADAT (SEQ ID NO: 58), and CDR3 is AKHHHRDDAFDV (SEQ ID NO: 59).
6. The chimeric antibody of claim 5 , wherein the light chain comprises the amino acid sequence of
(SEQ ID NO: 61)
MAWTPLLFLTLLLHCTGSLSQPVVTQSPSASASLGASVRLTCTLSSGRT
TFAVAWHQQQPQKAPRFLMRIYNDGSHFKGAGIPDRFSGSSSGAERYLT
ISSLQSDDEADYYCQTWGSGSVMFGGGTKVTVLG.
7. The chimeric antibody of claim 5 , wherein the heavy chain comprises the amino acid sequence of
(SEQ ID NO: 56)
MVIRTEQRELTMEFGLNWLFLVAILKGVQCEAQLFQSGGGLVQPGGSLR
LTCATSGFTFTNYALSWVRQAPGRGLEWVSSITDNADATYYADSVRGRF
TISRDNPKNTLYLQMDSLTAHDTAIYFCAKHHHRDDAFDVWGQGTMITV
SS.
8. The chimeric antibody of claim 5 , wherein the heavy chain comprises one or more of the following Fc mutations G236A, S239D, A330L, I332E, S267E, L328F, P238D, H268F, S324T, S228P, G236R, L328R, L234A, L235A, M252Y, S254T, T256E, M428L, and N434S
wherein the Fc mutations are in reference to following amino acid sequence starting at amino acid 119:
(SEQ ID NO: 179)
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVE
PKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWL
NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV
SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG.
9. A chimeric antibody that specifically binds HPV16 E2 protein wherein the antibody comprises a light chain and a heavy chain,
wherein the light chain CDR1 is VLPKKY (SEQ ID NO: 176), CDR2 is EDTK (SEQ ID NO: 177), and CDR3 is YSTDSSGNF (SEQ ID NO: 178); and
wherein the heavy chain CDR1 is GYDFAKYY (SEQ ID NO: 134), CDR2 is INPQNGVT (SEQ ID NO: 135), and CDR3 is NILYISGSNVWDY (SEQ ID NO: 136).
10. The chimeric antibody of claim 9 , wherein the light chain comprises the amino acid sequence of
(SEQ ID NO: 138)
MAWTPLLLPLLTFCTVSEASSELTQPPSVSVSPGQTARITCSGDVLPKK
YAYWYQQKSGQAPVLVVYEDTKRPSGIPERFSGSSSGTMATLTISGAQV
GDEGDYYCYSTDSSGNFFGGGTKLTVLG.
11. The chimeric antibody of claim 9 , wherein the heavy chain comprises the amino acid sequence of
(SEQ ID NO: 133)
MDWTWRVFCLLAVAPGAHSQVQMVQSGTEVKKPGASVKVSCKASGYDFA
KYYISWVRQAPGQGLEWMGMINPQNGVTTYTQKVQGRVTLTRDTSTTTV
YMELSSLRFEDTAVYYCNILYISGSNVWDYWGQGTLVTVSS.
12. The chimeric antibody of claim 9 , wherein the heavy chain comprises one or more of the following Fc mutations G236A, S239D, A330L, I332E, S267E, L328F, P238D, H268F, S324T, S228P, G236R, L328R, L234A, L235A, M252Y, S254T, T256E, M428L, and N434S
wherein the Fc mutations are in reference to following amino acid sequence starting at amino acid 119:
(SEQ ID NO: 179)
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV
HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVE
PKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD
VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWL
NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV
SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV
DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG.