On September 14, 2020 LAVA Therapeutics B.V., a biotech company pioneering bispecific gamma-delta T cell engagers for cancer, Amsterdam UMC and the Monash Biomedicine Discovery Institute in Australia, reported that Nature Cancer has published their co-authored paper titled, "A single domain bispecific antibody targeting CD1d and the NKT T cell receptor induces a potent antitumor response," detailing a novel immune-oncology approach for the potential treatment of cancer (Press release, Lava Therapeutics, SEP 14, 2020, View Source [SID1234565113]).
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Findings in the paper highlight the potential for a LAVA-derived antibody fragment, known as a single domain antibody, that acts as a bridge to link together two key immune cell receptors – the CD1d receptor and the T cell receptor of natural killer T (NKT) cells – in order to enhance the body’s immune response to cancer. The CD1d receptor is frequently expressed by tumor cells and NKT cells are positioned at the interface between the innate and adaptive immune system and play an important role in the host-rejection of both tumors and virally infected cells. Preclinical research through the companies’ collaboration demonstrates that a CD1d-NKT cell targeting antibody resulted in significant activation of NKT cells and the subsequent killing of CD1d-expressing tumor cells in multiple tumor samples, including multiple myeloma and acute myeloid leukemia.
"These data underscore the potential of LAVA’s bispecific antibody approach to target and activate NKT cells for the treatment of cancer," said Hans van der Vliet, professor in medical oncology at Amsterdam UMC and chief scientific officer of LAVA Therapeutics. "By targeting and boosting natural immune cells that are inherent in all humans, such as NKT and gamma-delta T cells, for an enhanced therapeutic effect, our approach could translate into a broadly applicable immunotherapeutic strategy for treating a range of cancer indications."
"Using the Australian Synchrotron, the team at Monash University provided detailed atomic insight into how the single domain antibodies exerted their effect on immune cells in a cancer model. Through this, we were able to precisely visualize how the single domain antibody simultaneously recognized CD1d and the NKT T cell receptor, thereby providing a molecular basis for their anti-tumor properties," professor Jamie Rossjohn, Australian Research Council Laureate Fellow at Monash University stated. "The collaboration with LAVA Therapeutics on this ground-breaking approach was very effective."
Instrumental to the study were joint first authors Dr. Roeland Lameris from Amsterdam UMC and Dr. Adam Shahine from Monash University.