CpG amphiphiles and uses thereof
The invention provides compounds including a CpG oligodeoxynucleotide sequence linked to a lipid by a linker and related compositions and methods. The invention features a compound consisting of the nucleotide sequence of SEQ ID NO:1, at its 5′ end, bonded or linked by a linker to a lipid. Further, the invention features a method of treating a cancer in a human patient, comprising administering to the patient the compound. Further, the invention features a pharmaceutical composition including the compound and a pharmaceutically acceptable carrier. The invention features a kit including (I) the compound or a composition comprising the compound; and (ii) a protein comprising SEQ ID NO:2 or SEQ ID NO:3.
1. A compound consisting of the nucleotide sequence 5′-TCGTCGTTTTGTCGTTTTGTCGTT-3′ (SEQ ID NO:1), at its 5′ end, bonded or linked by a linker to the following lipid:
or a salt thereof,
wherein X is O or S, and wherein the nucleotides in the nucleotide sequence are optionally joined by one or more phosphorothioate bonds.
2. The compound of claim 1 , wherein the nucleotide sequence is bonded to the lipid.
3. The compound of claim 1 , wherein all internucleoside groups connecting the nucleosides in 5′-TCGTCGTTTTGTCGTTTTGTCGTT-3′ (SEQ ID NO:1) are phosphorothioates.
4. A method of treating a human papillomavirus (HPV) positive cancer in a human patient comprising administering to the patient the compound of claim 1 , a protein comprising the amino acid sequence:
(SEQ ID NO: 2)
MHQKRTAMFQ DPQERPRKLP QLCTELQTTI HDIILECVYC
KQQLLRREVY DFAFRDLCIV YRDGNPYAVG DKCLKFYSKI
SEYRHYCYSL YGTTLEQQYN KPLCDLLIRC INGQKPLCPE
EKQRHLDKKQ RFHNGRGRWT GRCMSCCRSS RTRRETQL,
and a protein comprising the amino acid sequence:
(SEQ ID NO: 3)
MHGDTPTLHE YMLDLQPETT DLYGYGQLND SSEEEDEIDG
PAGQAEPDRA HYNIVTFCCK CDSTLRLCVQ STHVDIRTLE
DLLMGTLGIV CPICSQKP.
5. The method of claim 4 , wherein the cancer is HPV type 16 positive.
6. The method of claim 4 , wherein the cancer is a head or neck squamous cell carcinoma.
7. The method of claim 4 , wherein the patient is receiving or has received platinum-containing chemotherapy.
8. The method of claim 4 , wherein the compound and the proteins comprising the amino acid sequences of SEQ ID NO:2 and SEQ ID NO:3 are administered concurrently.
9. The method of claim 4 , wherein the compound and the proteins comprising the amino acid sequences of SEQ ID NO:2 and SEQ ID NO:3 are administered sequentially.
10. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
11. The pharmaceutical composition of claim 10 , wherein the composition further comprises a protein comprising the amino acid sequence:
(SEQ ID NO: 2)
MHQKRTAMFQ DPQERPRKLP QLCTELQTTI HDIILECVYC
KQQLLRREVY DFAFRDLCIV YRDGNPYAVG DKCLKFYSKI
SEYRHYCYSL YGTTLEQQYN KPLCDLLIRC INGQKPLCPE
EKQRHLDKKQ RFHNGRGRWT GRCMSCCRSS RTRRETQL,
and a protein comprising the amino acid sequence:
(SEQ ID NO: 3)
MHGDTPTLHE YMLDLQPETT DLYGYGQLND SSEEEDEIDG
PAGQAEPDRA HYNIVTFCCK CDSTLRLCVQ STHVDIRTLE
DLLMGTLGIV CPICSQKP.
12. A kit comprising (i) a compound of claim 1 , and (ii) a protein comprising the amino acid sequence:
(SEQ ID NO: 2)
MHQKRTAMFQ DPQERPRKLP QLCTELQTTI HDIILECVYC
KQQLLRREVY DFAFRDLCIV YRDGNPYAVG DKCLKFYSKI
SEYRHYCYSL YGTTLEQQYN KPLCDLLIRC INGQKPLCPE
EKQRHLDKKQ RFHNGRGRWT GRCMSCCRSS RTRRETQL,
and a protein comprising the amino acid sequence:
(SEQ ID NO: 3)
MHGDTPTLHE YMLDLQPETT DLYGYGQLND SSEEEDEIDG
PAGQAEPDRA HYNIVTFCCK CDSTLRLCVQ STHVDIRTLE
DLLMGTLGIV CPICSQKP.
13. A method of treating a human papillomavirus (HPV) positive cancer in a human patient comprising administering to the patient the compound of claim 2 , a protein comprising the amino acid sequence:
(SEQ ID NO: 2)
MHQKRTAMFQ DPQERPRKLP QLCTELQTTI HDIILECVYC
KQQLLRREVY DFAFRDLCIV YRDGNPYAVG DKCLKFYSKI
SEYRHYCYSL YGTTLEQQYN KPLCDLLIRC INGQKPLCPE
EKQRHLDKKQ RFHNGRGRWT GRCMSCCRSS RTRRETQL,
and a protein comprising the amino acid sequence:
(SEQ ID NO: 3)
MHGDTPTLHE YMLDLQPETT DLYGYGQLND SSEEEDEIDG
PAGQAEPDRA HYNIVTFCCK CDSTLRLCVQ STHVDIRTLE
DLLMGTLGIV CPICSQKP.
14. The compound of claim 2 , wherein all internucleoside groups connecting the nucleosides in 5′-TCGTCGTTTTGTCGTTTTGTCGTT-3′ (SEQ ID NO:1) are phosphorothioates.