Tag Archives: anti-PD1

𝗣𝘂𝗹𝗺𝗼𝗻𝗮𝗿𝘆 𝗔𝗿𝘁𝗲𝗿𝗶𝗮𝗹 𝗛𝘆𝗽𝗲𝗿𝘁𝗲𝗻𝘀𝗶𝗼𝗻 (𝗣𝗔𝗛) is a serious condition where the blood vessels in the lungs become narrowed, blocked or damaged. This restricts blood flow and places additional burden on the heart,. Over time, this increased workload can weaken the heart, leading to declining respiratory and cardiovascular function, significantly impacting the quality of life and, in severe cases, can be life-threatening.

The 𝗧𝗴𝟯𝟲𝟰𝟳 𝗵𝘂𝗺𝗮𝗻 𝗧𝗡𝗙 𝘁𝗿𝗮𝗻𝘀𝗴𝗲𝗻𝗶𝗰 𝗺𝗼𝘂𝘀𝗲 𝗺𝗼𝗱𝗲𝗹, carries a human TNF transgene with modified 3ʹ‐UTR rendering posttranscriptional regulation inactive. It was originally developed for arthritis research, but apart from inflammatory  polyarthritis, Tg3647 mice  develop progressive interstitial lung pathology with pathological findings of arteriole occlusion and right ventricular hypertrophy closely mirroring the human condition of Pulmonary Arterial Hypertension (PAH).

Therefore the Tg3647 mouse model can be identified as a suitable model to support better understanding of mechanisms underlying arthritis related cardiopulmonary pathologies and the development of therapeutics targeting these pathologies.

Walking on the side of researchers striving to establish an assay for the prediction of  the response of human lung cancer patients to cancer immunotherapy, we have established a 3D microfluidic tumour microculture system that involves the seeding of LLC (Lewis Lung Cancer) syngeneic mouse tumour aggregates in the central hydrogel channel of an Aim Microfluidic Chip  and the injection of anti-PD1 or anti-PDL1 antibodies in the two  flanking side channels.

Proteomics analysis  proteomics of the untreated vs anti-PD1 treated tumour samples revealed the signature of the response to treatment (A). Metascape analysis of increased  (B) or decreased ( C) protein expression after anti-PD1 treatment revealed the biological pathways involved.

With this data we have the proof of concept to support that a similar humanized PDL1/PD1 system can be used for screening the responses of human patients to anti-human PD1 therapeutics.

This work was performed under the European funded program “Next Generation EU” Greece 2.0, https://greece20.gov.gr/en/) BioOnChip, “Development of a Bronchoscopic Biopsies-On-Chip platform for immunotherapy drug screening in non-small cell lung cancer” that aimed to explore the applicability of an innovative 3D microfluidic microculture in predicting real-time responses to PD1-blockade in NSCLC patients, that, if efficient, might have important socioeconomic impact.