758 A phase 1 dose escalation and expansion study of the anti-CD200R1 antibody 23ME-00610 in patients with advanced solid malignancies

Rasco, Drew W.; Razak, Albiruni R. Abdul; Schmidt, Maike; Kell, Sariah A.; Glatt, Dylan M.; Belshaw, Erin; Majeed, Sophia R.; Kummar, Shivaani

doi:10.1136/jitc-2022-sitc2022.0758

Cited by 1 publication

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“…This led to the development of samalizumab (ALXN6000), a first-in-class anti-CD200 antibody tested in phase I clinical trials for multiple myeloma and chronic lymphocytic leukaemia by Alexion Pharmaceuticals [ 48 ]. In 2022, 23andMe announced the development of an anti-CD200R blocking antibody for use in solid cancers based on the findings of their proprietary genetic and health survey database [ 49 ], and a phase I clinical trial is now underway [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Combination CD200R/PD-1 blockade in a humanised mouse model

Fellermeyer

Anzilotti

Paluch

et al. 2023

Immunotherapy Advances

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There is an increasing number of immune-checkpoint inhibitors being developed and approved for cancer immunotherapy. Most of the new therapies aim to reactivate tumour-infiltrating T cells, which are responsible for the tumour killing. However, in many tumours, the most abundant infiltrating immune cells are macrophages and myeloid cells, which can be tumour-promoting as well as tumouricidal. CD200R was initially identified as a myeloid-restricted, inhibitory immune receptor, but was subsequently also found to be expressed within the lymphoid lineage. Using a mouse model humanised for CD200R and PD-1, we investigated the potential of a combination therapy comprising Nivolumab, a clinically approved PD-1 blocking antibody, and OX108, a CD200R antagonist. We produced Nivolumab as a murine IgG1 antibody and validated its binding activity in vitro as well as ex vivo. We then tested the combination therapy in the immunogenic colorectal cancer model MC38 as well as the PD-1 blockade-resistant lung cancer model LLC1, which is characterised by a large number of infiltrating myeloid cells, making it an attractive target for CD200R blockade. No significant improvement of overall survival was found in either model, compared to Nivolumab mIgG1 monotherapy. There was a trend for more complete responses in the MC38 model, but investigation of the infiltrating immune cells failed to account for this. Importantly, MC38 cells expressed low levels of CD200, whereas LLC1 cells were CD200-negative. Further investigation of CD200R blocking antibodies in tumours expressing high levels of CD200 could be warranted.

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Section: Discussionmentioning

confidence: 99%