Methods and reagents for the enhancement of virus transduction in the bladder epithelium
View Patent ↗Agents and methods for enhancing recombinant virus transduction in the bladder epithelium are described. A first method involves contacting the luminal surface of the bladder with a composition comprising a transduction enhancing agent and an oncolytic virus. Alternatively, the luminal surface of the bladder can be contacted first with a pretreatment composition comprising a transduction enhancing agent and, subsequently, with a composition comprising an oncolytic virus. Bladder treatment compositions comprising a transduction enhancing agent and an oncolytic virus are also described.
1. A method for treating superficial cancer of the bladder derived from the bladder epithelium, comprising:
contacting the luminal surface of the bladder with a pretreatment composition comprising a transduction enhancing agent; and
further contacting the luminal surface of the bladder with a composition comprising a replication competent oncolytic virus;
wherein cells of the bladder epithelium are transduced and the transduction enhancing agent has the following general formula (I):
wherein X is a sulfur or oxygen atom, each R 2 is independently hydrogen or a moiety represented by:
and R 1 represents an alkyl or alkenyl group of 12 carbons.
2. The method of claim 1 , wherein each R 2 is hydrogen.
3. The method of claim 1 , wherein the transduction enhancing agent has the chemical formula:
wherein n is 11.
4. The method of claim 1 , wherein the pretreatment composition comprises about 0.025 to about 0.4% by weight of the transduction enhancing agent.
5. The method of claim 1 , wherein the luminal surface of the bladder is contacted with the pretreatment composition for at least 20 minutes.
6. The method of claim 1 , wherein the luminal surface of the bladder is contacted with the composition comprising the replication competent oncolytic virus for 15 minutes or less.
7. The method of claim 1 , wherein the luminal surface of the bladder is contacted with the composition comprising the replication competent oncolytic virus for 10 minutes or less.
8. The method of claim 1 , wherein the transduction enhancing agent has the chemical formula:
wherein n is 6.
9. The method of claim 1 , wherein the oncolytic virus is an oncolytic adenovirus.
10. The method of claim 9 , wherein the oncolytic adenovirus is CG8840.
11. The method of claim 1 , wherein the oncolytic virus composition comprises at least 4×10 10 viral particles.
12. A method for transducing bladder epithelium cells, comprising:
contacting the luminal surface of the bladder with a pretreatment composition comprising a transduction enhancing agent; and
subsequently contacting the luminal surface of the bladder with a composition comprising a replication competent adenovirus;
wherein the transduction enhancing agent has the following general formula (I):
wherein X is an oxygen atom, and each R 2 is independently hydrogen or a moiety represented by:
wherein R 1 represents an alkyl or
alkenyl group of 12 carbons.
13. The method of claim 12 , wherein each R 2 is hydrogen.
14. The method of claim 12 , wherein the transduction enhancing agent has the chemical formula:
wherein n is 11.
15. The method of claim 14 , wherein the pretreating composition comprises about 0.025 to about 0.4% by weight of the transduction enhancing agent.
16. The method of claim 12 , wherein the transduction enhancing agent has the chemical formula:
wherein n is 6.
17. The method of claim 1 , wherein the luminal surface of the bladder is contacted with a pretreatment composition comprising a transduction enhancing agent and a replication competent adenovirus at the same time.
18. The method of claim 1 , wherein the luminal surface of the bladder is contacted with a pretreatment composition comprising a transduction enhancing agent prior to contact with a replication competent adenovirus.