Karin Gaensler, MD
Professor
As a physician-scientist and member of the Hematological Malignancies and Stem Cell Transplantation Program and Helen Diller Family Cancer Center at UCSF, my clinical focus has been the treatment of hematological malignancies, combining chemotherapeutic and autologous or allogeneic bone marrow/ stem cell transplantation approaches. My laboratory has focused on the development of gene transfer and stem cell transplantation approaches for the treatment of hematologic disorders, with a current focus on the development of immunotherapeutic approaches to treat minimal residual disease (MRD) in older patients with acute myelogenous leukemia (AML). There is a major clinical unmet need for effective and safe therapies to increase progression-free and overall survival in older individuals with leukemia whose prognosis is grim.
Compelling evidence for the efficacy of immunotherapy in eliminating minimal residual disease (MRD) is provided by the superior outcomes of allogeneic hematopoietic stem cell transplants (HSCT) due to graft vs leukemia (GVL) effects. However, patients > 60 yo are often ineligible for allo-HSCT. Two vaccine approaches are being developed as part of a collaborative consortium at UCSF, UCLA, UC Davis, and King’s College, London.
Our vaccine project focuses on genetic engineering of autologous whole cell AML vaccines to express CD80, and IL-15, and IL-15 Receptor alpha (IL-15Rα). The leukemia-specific cytolytic activity stimulated by engineered, irradiated AML cell vaccines expressing IL-15/IL-15Ra/CD80 was tested in the murine 32Dp210 myeloid leukemia model that recapitulates many features of human AML. Proof of concept (POC) studies showed that treatment of leukemia-bearing hosts induced superior anti-leukemic immunity when compared with vaccines expressing either CD80, or IL15-IL15Rα alone and eradicated leukemia 80% in leukemic mice an effect mediated by CD8+ T cells. (Shi, Y. et al (2018)).
Based on these proof of concept studies we received a Catalyst award through the CTSI at UCSF, a Translational Research Program grant from the Leukemia and Lymphoma Society in 2017, and a CIRM Translational-1 grant in 2018 to pursue non-overlapping studies with cGMP reagents supporting submission of a Pre-IND package to the FDA. Most recently, we were awarded a CIRM CLIN 1 grant (12/2022)to pursue IND enabling studies. These studies are being pursued as part of a collaborative consortium with investigators at UCSF (M. Rosenblum, L. Damon, A. Nambiar, A.Combes and K. Ganapathi), UCLA (Donald Kohn), and King's College London (Farzin Farzaneh).