Elicio Therapeutics and Moffitt Cancer Center are collaborating to characterize combination therapies pairing Elicio’s CD19 Amphiphile and a universal FITC Amphiphile with CD19 CAR T cells.
The research will be led by Marco Davila, associate member of the Blood and Marrow Transplant and Cellular Immunotherapies Department and Medical Director of Cell Therapies at Moffitt.
“Despite high initial response rates, patients with B-cell malignancies have limited durable long-term disease control,” Christopher Haqq, Elicio’s executive vice president, head of research and development, and chief medical officer, said in a statement.
Davila’s laboratory is uniquely positioned to evaluate lymph node targeted immunotherapy. His team evaluates CD19+ malignancies in mice with a normal immune system and normal lymph nodes, which is an advantage over more common mouse models conducted in immunosuppressed mice. Positive results would set the stage for clinical trials combining AMP-CD19 with marketed CD19 CAR T cells to increase response rate and durability.
“Our research, as well as research by other groups, suggest one avenue for improving outcomes for lymphoma patients treated with gene-engineered T cells is to combine this therapy with other agents to enhance response,” Davila said in a statement. “We believe the highly novel AMP vaccine holds great promise as a combination to increase the efficacy of T cells targeted to B cell malignancies and look forward to developing and evaluating this therapy at Moffitt.”
The AMP-CD19 is a CAR binding peptide modified to traffic into lymph nodes for display on native immune cells. AMP-CD19 can activate engineered T cells, enhance their persistence, and proliferation, as well as enhance their activity in treatment of B-cell malignancies including diffuse large B cell lymphoma and acute lymphocytic leukemia.
The AMP modification reprograms the biodistribution of peptides by the addition of an albumin binding and cell membrane insertion domain, which results in improved trafficking into lymph nodes where dendritic cells take in the peptides and present them to the CAR T receptors on the surface of T cells.
Elicio is broadly developing AMP technologies, with ELI-002 targeting solid tumors with mutated KRAS in oncology, the universal adjuvant ELI-004 (AMP-CpG) enhancing efficacy across oncology and infectious disease applications, and discovery programs identifying solid tumor AMP CAR T combinations. In addition, the combination of both Elicio’s Amphiphiles (AMPs) with CAR Ts led to synergy that enhanced solid tumor CAR T therapy in mice (Ma et al., 2019; Singh et al., 2019).
