Related Experiment Video
Updated: Apr 18, 2026
Ex vivo Expansion of Tumor-reactive T Cells by Means of Bryostatin 1/Ionomycin and the Common Gamma Chain Cytokines Formulation
Published on: January 14, 2011
Phase 1 Trial of Bi-shRNA STMN1 BIV in Refractory Cancer
Minal Barve1, Zhaohui Wang2, Padmasini Kumar3
1Mary Crowley Cancer Research Centers, Dallas, Texas, USA; Texas Oncology, P.A., Dallas, Texas, USA.
Abstract:
Stathmin1 (STMN1) is a microtubule modulator that is expressed in multiple cancers and correlates with poor survival. We previously demonstrated in vivo safety of bifunctional (bi) shRNA STMN1 bilamellar invaginated vesicle (BIV) and that systemic delivery correlated with antitumor activity. Patients with superficial advanced refractory cancer with no other standard options were entered into trial. Study design involved dose escalation (four patients/cohort) using a modified Fibonacci schema starting at 0.7 mg DNA administered via single intratumoral injection. Biopsy at baseline, 24/48 hours and resection 8 days after injection provided tissue for determination of cleavage product using next-generation sequencing (NGS) and reverse transcription quantitative polymerase chain reaction (RT-qPCR), 5' RLM rapid amplification of cDNA ends (RACE) assay. Serum pharmacokinetics of circulating plasmid was done. Twelve patients were entered into three dose levels (0.7, 1.4, 7.0 mg DNA). No ≥ grade 3 toxic effects to drug were observed. Maximum circulating plasmid was detected at 30 seconds with less than 10% detectable in all subjects at 24 hours. No toxic effects were observed. Predicted cleavage product was detected by both NGS (n = 7/7 patients analyzed, cohorts 1, 2) and RLM RACE (n = 1/1 patients analyzed cohort 3). In conclusion, bi-shRNA STMN1 BIV is well tolerated and detection of mRNA target sequence-specific cleavage product confirmed bi-shRNA BIV mechanism of action.
Insights
Bifunctional shRNA STMN1 bilamellar invaginated vesicles (BIV) demonstrated safety and confirmed mechanism of action in patients with advanced cancers. This novel therapy showed antitumor activity with no severe toxic effects observed.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Stathmin1 (STMN1) is a microtubule modulator overexpressed in various cancers, linked to poor patient survival.
- Previous studies confirmed the in vivo safety and antitumor activity of bifunctional (bi) shRNA STMN1 bilamellar invaginated vesicle (BIV) delivery.
Purpose of the Study:
- To evaluate the safety, tolerability, and mechanism of action of intratumoral bi-shRNA STMN1 BIV in patients with advanced, refractory cancers.
Main Methods:
- A dose-escalation Phase I clinical trial was conducted using a modified Fibonacci schema.
- Patients received single intratumoral injections of bi-shRNA STMN1 BIV at escalating doses (0.7, 1.4, 7.0 mg DNA).
- Tumor biopsies and serum samples were analyzed using next-generation sequencing (NGS), RT-qPCR, and 5' RLM RACE to confirm target engagement and pharmacokinetics.
Main Results:
- Twelve patients were enrolled across three dose cohorts; no drug-related adverse events of Grade 3 or higher were observed.
- Circulating plasmid levels peaked within 30 seconds and were <10% by 24 hours post-injection.
- The predicted mRNA cleavage product was detected in 7/7 patients by NGS and 1/1 patient by RLM RACE, confirming the bi-shRNA BIV mechanism of action.
Conclusions:
- Bi-shRNA STMN1 BIV is well-tolerated in patients with advanced cancers.
- The detection of the target cleavage product validates the drug's mechanism of action.
- This study supports further investigation of bi-shRNA STMN1 BIV as a potential cancer therapeutic.
Related Concept Videos
02:56Treatment Resistent Cancers
02:56Treatment Resistant Cancers
01:11Clinical Trials: Overview
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...