On June 13, 2023 Panbela Therapeutics Inc.,. (Nasdaq: PBLA), a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, reported that it has entered into a sponsored research agreement with The University of Texas MD Anderson Cancer Center for the evaluation of polyamine metabolic inhibitor therapies in combination with CAR-T cell therapies in preclinical models (Press release, Panbela Therapeutics, JUN 13, 2023, View Source;utm_medium=rss&utm_campaign=panbela-announces-sponsored-research-agreement-to-evaluate-polyamine-metabolic-inhibitor-therapy-in-combination-with-car-t-cell-therapy [SID1234632665]). The initial goal of these studies will be to ascertain if eflornithine and/or ivospemin treatment will augment CAR-T mediated cytotoxicity against CD19+ large B-cell lymphoma (LBCL) cell lines. Recently, a metabolite panel primarily consisting of polyamines was identified as predictive of poor response to anti-CD19 CAR T-cell therapy in relapsed refractory LBCL. Additionally, the polyamine (PA) uptake transport system is upregulated in LBCL and multiple myeloma (MM). Together, this suggests the potential for a polyamine targeted therapy in combination with CAR-T therapies.
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"While the literature has demonstrated the relationship between polyamines and the immune system, recent research shows that an elevated polyamine metabolic profile correlated to poor response to CAR-T cell therapy. This suggests that by combining our polyamine metabolic inhibitors, such as eflornithine and ivospemin, with CAR-T cell therapy it may overcome this resistance mechanism and have the potential to improve initial response rates and durability of response," said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. "Polyamine modulation of the immune system is an important focus for Panbela. With our first clinical proof of concept of polyamine targeted therapy in combination with a checkpoint inhibitor for patients with STK11 non-small cell lung cancer, we are excited for this research collaboration to now evaluate the potential benefit of polyamines in immune modulation for hematologic malignancies."
"There is a huge unmet need to improve CAR-T cell therapies for LBCL patients. Although the majority of LBCL patients can be cured with first-line therapy, the remaining ~40% will be refractory to or relapse from first-line therapy and have an average overall survival of ~6 months. Based on a recent publication by Fahrmann et al, an elevated polyamine metabolic blood signature correlated with poor response to therapy and elevated spermine synthase was prognostic for survival. Based on this data, we are excited to initiate our research collaboration to determine if modulating polyamines improves CAR-T cell activity preclinically with the hope that this may translate into a clinical benefit for LBCL patients and others with hematologic malignancies," said Elizabeth Bruckheimer, Ph.D. Vice President & Chief Scientific Officer of Panbela.