US2017306338A1PendingUtilityA1

Recombinant bacterium to decrease tumor growth

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Assignee: THE ARIZONA BOARD OF REGENTS FOR AND ON BEHALF OF ARIZONA STATE UNIVPriority: May 28, 2010Filed: Feb 3, 2017Published: Oct 26, 2017
Est. expiryMay 28, 2030(~3.8 yrs left)· nominal 20-yr term from priority
Inventors:Roy Curtiss, IiiWei Kong
C12N 1/36A61K 35/74C12N 15/74C12R 1/42C12R 2001/42C12N 1/205
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Claims

Abstract

The present invention encompasses a recombinant bacterium capable of reducing tumor growth.

Claims

exact text as granted — not AI-modified
1 . A recombinant bacterium, wherein the bacterium is capable of:
 a. increased expression of a nucleic acid encoding a chemoreceptor that directs chemotaxis towards tumors,   b. accumulation in a quiescent tumor,   c. hyper-invasion of a tumor,   d. reduced fitness in normal tissue,   e. enhanced stimulation of the host innate immune responses,   f. delivering a tumor specific DNA vaccine vector to a tumor cell, and   g. increased bacterium-induced host programmed cell death.   
     
     
         2 . A bacterium of  claim 1 , wherein the bacterium comprises the following mutations: ΔasdA27::TT araC P BAD  c2, ΔP murA25 ::TT araC P BAD  murA, Δ(wza-wcaM)-8, ΔrelA198::araC P BAD  lacI TT, Δ(araC P BAD )-18::P22 P R  araBAD, ΔpagP81::P lpp  lpxE, ΔendA2311[[1123]]. 
     
     
         3 . A bacterium of  claim 1 , wherein the bacterium comprises the following mutations: ΔP murA25 ::TT araC P BAD  murA, Δ(wza-wcaM)-8, ΔrelA198::araC P BAD  lacI TT, Δ(araC P BAD )-18::P22 P R  araBAD, ΔpagP81::P lpp  lpxE, ΔendA2311[[1123]], ΔP tar ::P trcΔlacO888  tar. 
     
     
         4 . A bacterium of  claim 1 , wherein the bacterium comprises the following mutations: ΔP murA25 ::TT araC P BAD  murA, Δ(wza-wcaM)-8, ΔrelA198::araC P BAD  lacI TT, Δ(araC P BAD )-18::P22 P R  araBAD, ΔpagP81::P lpp  lpxE, ΔendA2311[[1123]] ΔP tar ::P trc ΔlacO888  tar, ΔP tsr ::P trcΔlacO888  tsr. 
     
     
         5 . A bacterium of  claim 1 , wherein the bacterium comprises the following mutations: ΔP murA25 ::TT araC P BAD  murA, Δ(wza-wcaM)-8, ΔrelA198::araC P BAD  lacI TT, Δ(araC P BAD )-18::P22 P R  araBAD, ΔpagP81::P lpp  lpxE, ΔendA2311[[1123]], ΔP tar ::P trcΔlacO888 tar, ΔP tsr ::P trcΔlacO888  tsr, Δtrg, or ΔP trg ::rhaRS-P rhaB  trg. 
     
     
         6 . A bacterium of  claim 1 , wherein the bacterium comprises the following mutations: ΔP murA25 ::TT araC P BAD  murA, Δ(wza-wcaM)-8, ΔrelA198::araC P BAD  lac TT, Δ(araC P BAD )-18::P22 P R  araBAD, ΔpagP81::P lpp  lpxE, ΔendA2311[[1123]], ΔP tar ::P trcΔlacO888  tar, ΔP tsr ::P trcΔlacO888  tsr, Δtrg, or ΔP trg ::rhaRS-P rhaB  trg, ΔP hilA ::P trcΔlacO888  hilA. 
     
     
         7 . A bacterium of  claim 1 , wherein the bacterium comprises the following mutations: ΔP murA25 ::TT araC P BAD  murA, Δ(wza-wcaM)-8, ΔrelA198::araC P BAD  lacI TT, Δ(araC P BAD )-18::P22 P R  araBAD, ΔpagP81::P lpp  lpxE, ΔendA2311[[1123]], ΔP tar ::P trcΔlacO888  tar, ΔP tsr ::P trcΔlacO888  tsr, Δtrg, or ΔP trg ::rhaRS-P rhaB  trg, ΔP hilA ::P trcΔlacO888  hilA, ΔpurA. 
     
     
         8 . A bacterium of  claim 1 , wherein the bacterium comprises the following mutations: ΔasdA27::TT araC P BAD  c2, ΔP murA25 ::TT araC P BAD  murA, Δ(wza-wcaM)-8, ΔrelA198::araC P BAD  lacI TT, Δ(araC P BAD )-18::P22 P R  araBAD, ΔpagP81::P lpp  lpxE, ΔendA2311[[1123]], ΔP tar ::P trcΔlacO888  tar, ΔP tsr ::P trcΔlacO888  tsr, Δtrg, or ΔP trg ::rhaRS-P rhaB  trg, ΔP hilA ::P trcΔlacO888  hilA, ΔpurA, ΔP sopE2 ::P trc  sopE2. 
     
     
         9 . A bacterium of  claim 1 , wherein the bacterium comprises the following mutations: ΔasdA27::TT araC P BAD  c2, ΔP murA25 ::TT araC P BAD  murA, Δ(wza-wcaM)-8, ΔrelA 198::araC P BAD  lacI TT, Δ(araC PBAD)-18::P22 P R  araBAD, ΔpagP81::P lpp  lpxE, ΔendA2311[[1123]], ΔP tar ::P trcΔlacO888  tar, ΔP tsrΔlacO888  tsr, Δtrg, or ΔP trg ::rhaRS-P rhaB  trg, ΔP hilA ::P trcΔlacO888  hilA, ΔpurA, ΔP sopE2 ::P trc  sopE2, ΔP tlpA ::P ansB  tlpA. 
     
     
         10 . A recombinant bacterium, wherein the bacterium is capable of:
 a. regulated attenuation,   b. regulated lysis,   c. increased expression of a nucleic acid encoding a chemoreceptor that directs chemotaxis towards tumors,   d. accumulation in a quiescent tumor,   e. hyper-invasion of a tumor,   f. reduced fitness in normal tissue,   g. enhanced stimulation of the host innate immune responses,   h. delivering a tumor specific DNA vaccine vector to a tumor cell, and   i. increased bacterium-induced host programmed cell death.   
     
     
         11 . A method of inhibiting tumor growth, the method comprising administering a recombinant bacterium of  claim 1  to a tumor. 
     
     
         12 . A method of treating cancer in a subject, the method comprising administering a recombinant bacterium of  claim 1  to the subject, wherein the subject has cancer. 
     
     
         13 . A recombinant bacterium, wherein the bacterium is capable of:
 a. increased expression of Tar and Tsr, and   b. decreased expression of Trg.

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