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 comprising:
contacting a 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 adenovirus,
wherein the transduction enhancing agent is a disaccharide having a lipophilic side chain consisting of 12 carbons;
wherein said oncolytic adenovirus exhibits preferential expression in bladder epithelium;
and wherein said cancer is derived from the bladder epithelium.
2. The method of claim 1 , wherein 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.
3. The method of claim 2 , wherein the transduction enhancing agent has the chemical formula:
wherein n is 11.
4. The method of claim 1 , wherein the transduction enhancing agent has the chemical formula:
wherein n is 6.
5. The method of claim 4 , wherein the pretreatment composition comprises about 0.1% by weight of the transduction enhancing agent.
6. The method of claim 1 , wherein contacting the luminal surface of the bladder with the composition comprising the oncolytic adenovirus comprises delivering about 50 to about 500 ml of the composition comprising the oncolytic adenovirus to the bladder by instillation.
7. The method of claim 1 , wherein the oncolytic adenovirus composition comprises from about 1×10 11 to about 1×10 14 viral particles.
8. The method of claim 1 , wherein contacting the luminal surface of the bladder with a pretreatment composition comprises delivering the pretreatment composition to the bladder by instillation.
9. The method of claim 1 , further comprising washing the luminal surface of the bladder after contact with the pretreatment composition and before contact with the composition comprising the oncolytic adenovirus.
10. The method of claim 1 , wherein the pretreatment composition is contacted with the luminal surface of the bladder for about 5 minutes.
11. The method of claim 1 , wherein the pretreatment composition further comprises an oxidizing agent.
12. The method of claim 11 , wherein the oxidizing agent is selected from the group consisting of hypochlorous acid, hydrogen peroxide, and peroxyacetic acid.
13. A composition comprising:
a transduction enhancing agent; and
a replication competent oncolytic adenovirus;
wherein said replication competent oncolytic adenovirus is effective to transduce cells of a bladder epithelium and said 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.
14. The composition of claim 13 wherein the transduction enhancing agent has the chemical formula
wherein n is 11.
15. The composition of claim 13 wherein the transduction enhancing agent has the chemical formula
wherein n is 11.
16. A composition comprising:
a transduction enhancing agent; and
a replication competent oncolytic adenovirus;
wherein said replication competent oncolytic adenovirus is effective to transduce cells of a bladder epithclium and said transduction enhancing agent has the following formula
wherein n is 6.
17. A composition comprising:
a transduction enhancing agent; and
a replication competent oncolytic adenovirus;
wherein said replication competent oncolytic adenovirus is effective to transduce cells of a bladder epithelium and said transduction enhancing agent has the following formula
wherein n is 6.
18. The method of claim 2 , wherein the transduction enhancing agent has the chemical formula:
wherein n is 11.
19. The method of claim 1 , wherein the transduction enhancing agent has the chemical formula:
wherein n is 6.
20. The method of claim 1 , wherein the composition comprising the transduction enhancing agent and the composition comprising the replication competent oncolytic adenovirus are co-administered.
21. The method of claim 1 , wherein the composition comprising the transduction enhancing agent is administered prior to the composition comprising the replication competent oncolytic adenovirus.
22. The method of claim 4 or claim 19 , wherein the pretreatment composition comprises about 0.1% by weight of the transduction enhancing agent.