University of Calgary
Project Term: July 1, 2023 - June 30, 2026
Novel immune approaches have revolutionized the treatment paradigms in multiple myeloma (MM) with deep responses seen in heavily pretreated patients. However responses are largely not durable with significant gaps remaining in our understanding of the mechanisms mediating the immune escape to to CAR T cells and T cell engagers. Harnessing the power of single cell immunogenomics and building on the knowledge we amassed to date, we plan to address these therapeutics and mechanistic challenges firstly through the informed design and clinical development of a BCL2L1 armoured BCMA-targeting CAR T cell, and secondly by establishing a dictionary of the MM-TME interactome through serial interrogation of primary MM cells and their immunome generating a dynamic risk prediction model to better guide the delivery of immuno-therapeutics.
A resurgence of cancer immune based therapeutics paralleled by leap advances in single cell genomics has led to unprecedented responses in cancer. Multiple myeloma (MM) a clonal malignancy of mature immune B-cells aka plasma cells, has also benefited from the introduction engineered immune T cells (CART) and bispecific antibodies with very promising, but not yet curative responses. Large gaps also remain in our understanding of the mechanisms mediating resistance to immune therapies. To help decipher these mechanisms and better the development of the next generation of these immune therapeutics our group has interrogated at the single cell level the genomics of the immune environment as well as MM cells. These studies have provided us with key leads to design and develop a novel armored CAR T cell with remarkable preclinical activity. The current project focuses on the development of this novel CAR T cell and the establishment of dynamic predictive model of response to immune therapies