The CIRM Alpha Stem Cell Clinic at UC San Diego has made several clinical trial advances in cancer, spinal cord injury, diabetes and heart failure. The main goal has been to establish safety, tolerability and proof of efficacy and we have transitioned a number of these trials to the proof of efficacy phases.
Stem Cell Gene Therapy for Inherited Disorders
A Phase 1, first-in-human CIRM funded clinical trial was launched at UCSD with Alpha Clinic support based on research conducted by UCSD’s Stephanie Cherqui and Edward Ball, and Donald Kohn (UCLA). This ex vivo transduced autologous human CD34+ hematopoietic stem cells for treatment of cystinosis culminated is an actively enrolling clinical trial at UCSD with Alpha Clinic support.
Cancer Stem Cell Targeting with Cirmtuzumab
As a result of encouraging phase 1 safety and proof-of-concept data, Cirmtuzumab partnered with Oncternal Therapeutics Inc. and through the CIRM Alpha Stem Cell Clinic launched a CLIN2 grant-funded trial (PI Kipps, Trial PIs Jamieson and Choi). This Phase 1b/2 trial of Cirmtuzumab combined with Ibrutinib focuses on assessing safety and efficacy in patients with refractory B cell malignancies. The phase 1 results of this trial showed that decreased chronic lymphocytic leukemia (CLL) burden and delayed time to next treatment coincided with reversal of the stemness index and reversion to more normal hematopoiesis RNA sequencing signatures. The Phase 2 trial for CLL and Mantle Cell Lymphoma (MCL) of Cirmtuzumab combined with ibrutinib has expanded to include other Alpha Stem Cell Clinic sites. We launched a Phase 1b/2a breast cancer study in combination with placlitaxel with Oncternal providing Cirmtuzumab and with co-funding from the Moores Cancer Center and more recently a state grant to treat underrepresented minority (URM) populations.
T cell and iPS NK Cell Immunotherapy to Target Pre-Cancer and Cancer
A first-in-human Phase 1 study of induced pluripotent stem cells (iPS) derived NK cells sponsored by FATE therapeutics has been launched for patients with advanced solid tumors. In addition, we are expanding the Aivita sponsored dendritic cell vaccine trials for glioblastoma multiforme (GBM) to ovarian cancer at UC San Diego and via an IRB reliance agreement with UCI’s Alpha clinic. To support these complex trials, we have also established a dedicated cell and regenerative medicine service (CRM) to ensure that patients are carefully monitored for immune-based adverse events both as inpatients and as outpatients.
A phase 1 trial of personalized, adoptive immunotherapy by cytotoxic T cells (CTLs) targeted to Myelodysplastic syndromes (MDS)-specific pre-cancer stem cell neoantigens is enrolling patients and is sponsored by Persimmune. This is a paradigm shifting and practice changing cancer prevention strategy that has the potential to reduce the number of cases that advance to full blown acute myeloid leukemia (AML). As a result of marrying cancer center activities to stem cell research activities it is possible to address an unmet medical need in a logical and safe manner.
Neural Stem Cell Regeneration and Repair
We completed a Phase 1 trial to evaluate safety and tolerability of a neural stem cell product sponsored by Neuralstem for chronic thoracic spinal cord injury patients. Proof-of-concept studies to evaluate neural repair and regeneration, including quantitative DT imaging and EMG measurements of recovery of neuronal function, showed early evidence of spinal cord remyelination. This trial has also helped to hone the requisite clinical trial expertise for initiating other acute spinal cord injury trials at UC San Diego including the enhancement of endogenous repair with scaffold with In Vivo. We have added to the interventional neurological repair portfolio by initiating the Discgenics-sponsored trial of MSCs for single level disc herniation.
Stem Cell Derived Therapy for Metabolic Disorders
Two Phase 1/2 trials to evaluate a device (EncaptraTM) containing human pluripotent stem cell derived pancreatic precursors, and a related device (PEC-Direct) are ongoing at UC San Diego. Treated patients at the UCSD Alpha Stem Cell Clinic are monitored for safety, tolerability and biomarkers of response. These studies are supported by ViaCyte, Inc., CIRM Strategic Partnership and CLIN2 awards as well as the Sanford Stem Cell Clinical Center.
Immunomodulatory Mesenchymal Stromal Cell Therapy
A phase 3 trial to establish efficacy of a mesenchymal stromal cell (MSC) product is currently being evaluated in patients with advanced congestive heart failure. As a result of Alpha Stem Cell Clinic involvement, accrual has increased on the trial at UC San Diego. The trial is sponsored by Mesoblast and has provided the impetus for developing stem cell and immune cellular imaging reagents for MRI detection developed by CIRM funded Professor Erich Ahrens and Nobel Laureate, Professor Roger Tsien.