Friday, March 10, 2017 11:46:27 AM
AbstractAggressive non-Hodgkin's lymphoma (NHL) progresses rapidly. It makes up about 60% of all NHL cases in the United States. The chemotherapy regimen R-CHOP could cure up to 70% of patients with aggressive NHL. Nonetheless, up to 30% of patients with aggressive NHL relapse from R-CHOP within 2 years of initial treatment. Novel therapeutics are urgently needed for patients with relapsed, aggressive NHL. Bcl-2 is a potential therapeutic target for aggressive NHL because high expression of Bcl-2 has been reported in NHL and correlated with adverse prognosis for NHL patients. To inhibit the expression of Bcl-2 protein, BP1002 was developed. BP1002 is comprised of an uncharged P-ethoxy antisense oligodeoxynucleotide targeted against Bcl-2 mRNA. The P-ethoxy antisense backbone does not have an adverse effect on bleeding and complement activation, which are some of the toxicities that have been reported for other antisense analogs. The Bcl-2 antisense is incorporated in neutral liposomes so that it can be delivered systemically via intravenous infusion. The inhibitory activity of BP1002 was determined in human lymphoma cell lines, which included germinal center B-cell (GCB) diffuse large B cell lymphoma (DLBCL), activated B-cell (ABC) DLBCL, mantle cell lymphoma (MCL) and Burkitt’s lymphoma (BL). The lymphoma cell lines were incubated with BP1002 for four days. The sulforhodamine B cytotoxicity assay showed that BP1002, at 200 micrograms/mL, induced ≥50% inhibition in 5 of 8 GCB DLBCL lines, 3 of 3 ABC DLBCL lines, 1 of 1 MCL line, and 1 of 1 BL line. We also determined the activity of BP1002 in animal models. Severe combined immunodeficiency (SCID) mice were implanted with CJ cells, which are transformed follicular lymphoma cells that express high levels of Bcl-2 protein. In experiment I, 4 groups of mice were used: Group 1 - untreated mice; Group 2 - mice treated with 10 mg of BP1002 per kg of mouse body weight; Group 3 - mice treated with 20 mg of BP1002 per kg of mouse body weight; Group 4 - mice treated with control empty liposomes equivalent to 20 mg/kg of BP1002. One week after tumor implantation, mice were injected with BP1002 or empty liposomes intravenously twice per week. When mice were euthanized in week 5, all untreated mice and mice treated with control empty liposomes reached moribund state. However, no mouse in the BP1002 treatment groups reached moribund state. In experiment II, 3 groups of mice were used: Group 1 - untreated mice; Group 2 - mice treated with 20 mg/kg of liposome-incorporated control oligodeoxynucleotide; Group 3 - mice treated with 20 mg/kg of BP1002. All untreated mice and control mice were moribund in week 5, but only 40% of BP1002-treated mice were moribund. These in vivo experiments indicate that BP1002 could extend the survival of mice bearing aggressive NHL. Together, our data indicate that BP1002 is a novel therapeutic for aggressive NHL.
Recent BPTH News
- Bio-Path Holdings, Inc. Announces Closing of $1.2 Million Registered Direct Offering Priced At-the-Market Under Nasdaq Rules • GlobeNewswire Inc. • 04/19/2024 04:14:04 PM
- Bio-Path Holdings, Inc. Announces $1.2 Million Registered Direct Offering Priced At-the-Market Under Nasdaq Rules • GlobeNewswire Inc. • 04/18/2024 05:57:59 PM
- Bio-Path Holdings Announces Successful Completion of Higher Dose Second Cohort in Phase 1/1b Clinical Trial of BP1002 in Refractory/Relapsed Acute Myeloid Leukemia (AML) Patients • GlobeNewswire Inc. • 04/18/2024 11:00:00 AM
- Bio-Path Holdings Expands Global Patent Portfolio • GlobeNewswire Inc. • 04/15/2024 11:00:00 AM
- Bio-Path Holdings Provides 2024 Clinical and Operational Update • GlobeNewswire Inc. • 04/02/2024 11:00:00 AM
- Form 8-K - Current report • Edgar (US Regulatory) • 03/11/2024 11:00:34 AM
- Form S-1 - General form for registration of securities under the Securities Act of 1933 • Edgar (US Regulatory) • 03/08/2024 10:11:50 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 03/08/2024 12:10:34 PM
- Bio-Path Holdings Reports Full Year 2023 Financial Results • GlobeNewswire Inc. • 03/08/2024 12:00:00 PM
- U.S. Index Futures Fluctuate Ahead of Key Jobs Report; Oil Prices Dip • IH Market News • 03/08/2024 11:22:25 AM
- Form 10-K - Annual report [Section 13 and 15(d), not S-K Item 405] • Edgar (US Regulatory) • 03/07/2024 09:21:27 PM
- Bio-Path Holdings to Announce Fourth Quarter and Full Year 2023 Financial Results on March 8, 2024 • GlobeNewswire Inc. • 03/01/2024 12:00:00 PM
- Form RW - Registration Withdrawal Request • Edgar (US Regulatory) • 02/29/2024 11:00:30 AM
- Form 8-K - Current report • Edgar (US Regulatory) • 02/23/2024 12:01:09 PM
- Bio-Path Holdings Announces 1-for-20 Reverse Stock Split • GlobeNewswire Inc. • 02/21/2024 12:00:00 PM
- Form SC 13G - Statement of acquisition of beneficial ownership by individuals • Edgar (US Regulatory) • 02/02/2024 09:39:37 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 02/02/2024 09:10:23 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 01/23/2024 10:20:23 PM
- Form S-1/A - General form for registration of securities under the Securities Act of 1933: [Amend] • Edgar (US Regulatory) • 01/23/2024 09:51:03 PM
- Form DEFA14A - Additional definitive proxy soliciting materials and Rule 14(a)(12) material • Edgar (US Regulatory) • 01/17/2024 09:52:48 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 01/10/2024 09:10:09 PM
- Bio-Path Holdings Announces Completion of First Dose Cohort in Phase 1 Clinical Trial Evaluating BP1002 to Treat Refractory/Relapsed Lymphoma and Refractory/Relapsed Chronic Lymphocytic Leukemia Patients • GlobeNewswire Inc. • 01/10/2024 12:00:00 PM
- Form DEF 14A - Other definitive proxy statements • Edgar (US Regulatory) • 01/04/2024 10:18:53 PM
- Form PRE 14A - Other preliminary proxy statements • Edgar (US Regulatory) • 12/22/2023 09:06:16 PM
- Form S-1 - General form for registration of securities under the Securities Act of 1933 • Edgar (US Regulatory) • 12/22/2023 09:05:51 PM
NanoViricides Reports that the Phase I NV-387 Clinical Trial is Completed Successfully and Data Lock is Expected Soon • NNVC • May 2, 2024 10:07 AM
ILUS Files Form 10-K and Provides Shareholder Update • ILUS • May 2, 2024 8:52 AM
Avant Technologies Names New CEO Following Acquisition of Healthcare Technology and Data Integration Firm • AVAI • May 2, 2024 8:00 AM
Bantec Engaged in a Letter of Intent to Acquire a Small New Jersey Based Manufacturing Company • BANT • May 1, 2024 10:00 AM
Cannabix Technologies to Deliver Breath Logix Alcohol Screening Device to Australia • BLO • Apr 30, 2024 8:53 AM
Hydromer, Inc. Reports Preliminary Unaudited Financial Results for First Quarter 2024 • HYDI • Apr 29, 2024 9:10 AM