A Novel Immune Modulating Antibody for the Treatment of Lung Cancer
Abstract
GT103 is an anti-complement factor H (CFH) mAb that kills tumor cells by complement dependent cytotoxicity (CDC), and inhibits the growth of tumors while stimulating an immune response. Our overall project objectives are to determine howGT103 causes tumor growth inhibition in mice and to define a cancer patient population who will best respond to GT103 as a cancer treatment. Our Specific Aims are: 1. Investigate the in vivo impacts of GT103 treatment on innate immune pathways;2.Investigate antigen presentation and adaptive immunity in GT103 cancer immunotherapy; 3. Define a cancer patient population most amenable to GT103 treatment. In this first year of the grant, we have focused on Aims 1 and 2. We found thatGT103 induces CDC by both the alternative and classical complement pathways, which suggests that GT103 does not only block CFH but may form immune complexes that could engage immune cells. In CMT167 subcutaneous lung tumor-bearingC57BL/6 mice, GT103 reduces the number of intratumoral immunosuppressive T regulatory cells and myeloid-derived suppressor cells and increases the number of intratumoral immune-modulatory dendritic cells over control. We discovered that multiple gene expression pathways were upregulated in the tumors of GT103 treated tumor bearing mice, including those for B-cell receptor signaling, regulation of cell-cell adhesion, leukocyte chemotaxis, regulation of Interleukin-1 production, leukocyte migration, regulation of IFN production, regulation of cell activation, and cell chemotaxis. In addition, we found that in the B16F10 melanoma model, GT103 and anti-PD-1 acted synergistically to suppress tumor growth. Future work will focus on integrating these findings with a focus on B cell- and T cell-mediated mechanisms of adaptive immunity, as well as beginning to study human correlates to our findings in mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2020
- Accession Number
- AD1111617
Entities
People
- Edward F. Patz
Organizations
- Duke University