Methods employing gaseous nitric oxide for inhibiting tumor growth
Methods of inhibiting growth of cells or tissue of a primary and/or secondary tumor, and/or of stimulating an immunological response to the tumor, in a subject in need thereof, and systems for performing same, are provided. The methods employ local administration of a gas, such as gaseous nitric oxide, typically at a high dose. Immune cells obtained upon treating a tumor with gaseous nitric oxide, either in vivo or ex vivo, and methods employing same are also provided.
1 . A method of inhibiting growth of cells or tissue of a primary and/or secondary tumor in a subject in need thereof, the method comprising locally administering to the tumor gaseous nitric oxide (gNO) at a dose of from about 1,000 ppm to about 1,000,000 ppm for a time period of from about 1 second to about 60 minutes at a volumetric flow of from about 0.00001 LPM to about 1 LPM, wherein locally administering said gNO is by intratumoral injection.
2 . The method according to claim 1 , wherein the gNO is administered at a dose of from about 20,000 ppm to about 200,000 ppm or from about 20,000 ppm to about 50,000 ppm.
3 . The method according to claim 1 , wherein the gNO is administered for a time period that ranges from about 30 seconds to about 10 minutes.
4 . The method according to claim 1 , wherein the gNO is administered at a volumetric flow of from about 0.001 LPM to about 0.5 LPM.
5 . The method according to claim 1 , wherein the gNO is administered at two or more administration sites in the tumor.
6 . The method according to claim 5 , wherein the distance between the two or more administration sites is, independently, from about 2.5 mm to about 1 cm, or from about 0.25 cm to about 0.5 cm.
7 . The method according to claim 1 , wherein the gNO is administered at a dose of from about 0.1 mg to about 300 mg, per cm 3 tumor.
8 . The method according to claim 1 , wherein gNO is administered at a dose of from about 0.01 mg to about 100 mg, or from 0.1 mg to about 10 mg, per a tumor of 20 mm 3 or less.
9 . The method according claim 1 , further comprising scavenging excess gNO from the administration site.
10 . The method according to claim 1 , wherein locally administering said gNO is pulsed from about 2 to about 20 times.
11 . The method according to claim 1 , wherein locally administering said gNO to the subject is performed at least once.
12 . The method according to claim 1 , wherein locally administering said gNO to the subject is performed at least twice, and wherein a time interval between said two administrations is at least one week.
13 . The method according to claim 1 , further comprising co-administering to the subject an anti-cancer therapy.
14 . The method according to claim 1 , being for inhibiting growth and/or killing cells of a primary tumor.
15 . The method according to claim 1 , being for preventing occurrence, inhibiting growth and/or killing cells of a secondary tumor.
16 . The method according to claim 1 , wherein said secondary tumor comprises metastasizing tumor and/or a recurrent tumor.
17 . The method according to claim 1 , being for stimulating in the subject an immunological response to the tumor, thereby inhibiting growth of a primary tumor and/or a secondary tumor.