Lava Therapeutics B.V. is a start-up biotechnology company, founded in 2016, that creates and develops next generation γδ T cell engaging bispecific antibodies for the treatment of cancer. Our first-in-class immuno-oncology approach activates γδ T cells in a tumor target dependent manner.
The objective of Lava Therapeutics B.V is to develop potent, safe and cost-effective biopharmaceuticals that arm the immune system to recognize and destroy tumor cells.
Paul Parren is an expert in antibody research, translational science and drug development. He is a professor of molecular immunology at the Leiden University Medical Center.
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T lymphocytes are divided in two main categories based on T cell receptor type; αß and γδ T cells. Whereas αß T cells have specific reactivity to peptides presented via HLA antigens, γδ T cells are activated by non-peptide antigens. Human γδ T cells are classified based on their receptor Vδ chain, with Vγ9Vδ2 T cells being the predominant subpopulation in circulation. These Vγ9Vδ2 T cells represent a potent class of proinflammatory immune effector cells with an immune surveillance function. Vγ9Vδ2 T cells are able to sense the presence of small phosphorylated metabolite antigens termed phosphoantigens, which are often expressed at high levels by tumor cells. Binding of the γδ T cell receptor to the butyrophilin-phosphoantigen complex leads to Vγ9Vδ2 T cell activation, tumor cell killing, secretion of pro-inflammatory cytokines and tumor-infiltration. In addition, these cells can act as antigen-presenting cells, priming the adaptive immune system.
Vγ9Vδ2 T cells can provide effective anti-tumor immune responses against both solid and haematological malignancies. The presence of Vγ9Vδ2 T cells correlates with increased survival for a wide range of cancers (Tosolini M. et al. 2017). Interestingly, Vγ9Vδ2 T cells, in contrast to αβ T cells, infiltrate tumors independent of mutational tumor load.
Support for the potential of γδ T cell-based therapies is provided by Buccheri S. et al. 2014, showing favourable clinical outcomes and low toxicity in a meta-analysis of γδ T cell-based immunotherapies both performed by adoptive cell therapies and in vivo activation with compounds such as synthetic γδ T cell ligands or aminobisphosphonates.
LAVA’s bispecific γδ T cell engagers uniformly and specifically bind to the conserved T cell receptor of Vγ9Vδ2 T cells, providing a tumor target dependent response, avoiding generalized T cell activation known to induce side effects.
Proof of principle has been established by in vitro and in/ex vivo studies in which Vγ9Vδ2 T cell engagers demonstrate potent tumor lysis of both tumor cell lines and primary patient materials.
The company is currently working on several lead bispecific Vγ9Vδ2 T cell engager candidates that are progressing towards the clinic.
Lava develops proprietary bispecific Vγ9Vδ2 T-cell engagers for selected tumor targets. Pharmaceutical companies with an interest to use Lava’s Vγ9Vδ2 T-cell engagers for own tumor targets or with an interest in Lava’s lead projects should contact Lava via info@lavatherapeutics.com.
Collaborations are a key part of our business strategy and we are actively seeking new partnerships with companies that are interested in licensing our products and proprietary technologies.
Lava Therapeutics is always on the lookout for talented people with an entrepreneurial mindset.
If you feel excited about contributing to the development of novel cancer treatments based on our first in class γδ T cell engaging bispecific antibodies, let us know.
Application letters can be sent to info@lavatherapeutics.com
