CCBIO seminar: Øystein Rekdal
From bench to bedside with a first in class oncolytic peptide
Lytix Biopharma AS, Oslo, and Department of Medical Biology, The Arctic University of Norway, Tromsø
The oncolytic peptide LTX-315 has been designed de novo based on structure-activity relationship studies of host defense peptides. This peptide has the ability to kill human cancer cells and induce a specific anticancer immune response when injected locally into tumors established in immunocompetent mice. The oncolytic effect of LTX-315 involves perturbation of the plasma membrane and the mitochondria with subsequent release of danger-associated molecular pattern molecules and tumor antigens which highlights the ability of LTX-315 to induce complete regression and protective immune responses. Systemic efficacy can be enhanced in vivo by combination with several other types of cancer therapies.
Clinical safety has been demonstrated as a single agent administered intratumorally in a phase I study. Best overall response seen in cancer patients was stable disease (SD). However, in several patients a marked tumor regression was observed in distant non-injected lesions. LTX-315 monotherapy resulted in increased number of cytotoxic CD8+ T cells in the majority of treated lesions. T cell receptor (TCR) sequencing revealed a systemic clonal expansion of T cells after LTX-315 treatment.
The clinical results generated demonstrate the potential of LTX-315 as a primer of tumor specific T cells, making it ideal for combination with other immunotherapies.
Chairperson: Bjørn Tore Gjertsen, CCBIO