Invited Lecture: Local delivery of anti-PD-L1 nanobodies overcomes poor antibody penetration and allows improved blocking of PD-L1 at the tumor site
(2021) 5th Annual MarketsandMarkets Next Gen Immuno-Oncology Virtual Congress (26.October.2021)
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- Abstract
- Monoclonal antibodies blocking immune checkpoints such as PD-L1 have brought strong clinical benefits in many cancer types. Still, the current limitations are the lack of clinical response in a majority of patients and the development of immune-related adverse events in some of them. As an alternative to anti-PD-L1 antibody injection, we developed an approach based on the engineering of tumor-targeting T cells to deliver intratumorally an anti-PD-L1 nanobody. In the MC38-OVA model, our strategy enhanced tumor control as compared to injection of anti-PD-L1 antibody combined with adoptive transfer or tumor-targeting T cells. Furthermore, we demonstrate the detrimental distribution pattern of anti-PD-L1 antibody which massively occupies PD-L1 in the periphery but fails to penetrate at the tumor site. In sharp contrast, locally delivered anti-PD-L1 nanobody improved PD-L1 blocking at the tumor site while avoiding systemic exposure. Our approach appears promising to overcome the limitations of immunotherapy based on anti-PD-L1 antibody treatment.
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Citations
Zhu, J. (2021). Invited Lecture: Local delivery of anti-PD-L1 nanobodies overcomes poor antibody penetration and allows improved blocking of PD-L1 at the tumor site. 5th Annual MarketsandMarkets Next Gen Immuno-Oncology Virtual Congress. https://hdl.handle.net/2078.5/113206