Targeting Bcl-2 with Antisense Therapy in Aggressive NHL: A Novel Approach to Overcome Relapse

Aggressive non-Hodgkin's lymphoma (NHL) is a rapidly progressing cancer, accounting for 60% of NHL cases in the United States. While R-CHOP chemotherapy can cure a majority of these patients, a significant 30% relapse within two years, highlighting the need for new treatments. Bcl-2, a protein overexpressed in NHL and associated with poor outcomes, presents a promising therapeutic target.

BP1002 is an uncharged P-ethoxy antisense oligodeoxynucleotide that targets Bcl-2 mRNA, designed to inhibit Bcl-2 protein expression without the adverse effects associated with other antisense agents. Encapsulated in neutral liposomes for systemic intravenous delivery, BP1002's efficacy was tested on various human lymphoma cell lines, including GCB DLBCL, ABC DLBCL, MCL, and BL. After a four-day incubation, BP1002 demonstrated significant inhibitory effects at a concentration of 200 micrograms/mL.

Further studies in SCID mice implanted with Bcl-2 expressing CJ cells showed that BP1002 treatment significantly extended survival rates compared to untreated mice or those treated with control liposomes. In a second experiment, BP1002 again showed a survival advantage, with only 40% of treated mice becoming moribund by week 5, compared to all control mice.

The collective findings suggest that BP1002 is a potential novel therapeutic agent for treating aggressive NHL, offering a new strategy for patients who have relapsed after initial R-CHOP treatment.