{"entity":{"id":"idea-cd8-pet-io","kind":"idea","name":"CD8 PET to stop or switch immunotherapy early","aka":[],"tldr":"Scan for T cells inside the tumour a few weeks after starting immunotherapy. If they have not arrived, change course.","summary":"Scan for T cells inside the tumour a few weeks after starting immunotherapy, and change course if they have not arrived. Tracers such as 89Zr-crefmirlimab, a CD8 minibody, and 18F-AraG image T-cell infiltration and activation, and an early increase has tracked response in phase 2 studies. Response to checkpoint blockade requires T-cell infiltration, CT changes lag by months and pseudoprogression confounds RECIST, so an absent CD8 PET signal at week 4 could identify non-responders early. The test is a prospective trial in NSCLC or melanoma with week-4 CD8 PET, randomising PET non-responders to continue or switch. At early-clinical maturity it addresses the bottleneck No one can predict who responds to immunotherapy.","asOf":"2026-09-04","links":[{"label":"Farwell et al., CD8-targeted PET imaging of tumour-infiltrating T cells in patients with cancer: a phase 1 first-in-human study of 89Zr-Df-IAB22M2C (Journal of Nuclear Medicine 2021)","url":"https://doi.org/10.2967/jnumed.121.262485"}],"tags":[],"related":[],"cancers":["melanoma","nsclc"],"sections":[],"technologies":["immuno-pet","checkpoint-inhibitor"],"targets":["pd1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-farwell-j-nucl-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Absence of CD8 PET increase at week 4 identifies non-responders with >85% specificity, enabling early switch to alternative therapy.","rationale":"Response to checkpoint blockade requires T-cell infiltration; CT changes lag by months; pseudoprogression confounds RECIST.","test":"Run a prospective trial in NSCLC or melanoma with week-4 CD8 PET; randomise PET-non-responders to continue vs switch.","maturity":"early-clinical"},"route":"/ideas/idea-cd8-pet-io/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"immuno-pet","kind":"technology","name":"Immuno-PET","route":"/technologies/immuno-pet/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"paper":[{"id":"paper-farwell-j-nucl-med","kind":"paper","name":"CD8-Targeted PET Imaging of Tumor-Infiltrating T Cells in Patients with Cancer: A Phase I First-in-Humans Study of 89 Zr-Df-IAB22M2C, a Radiolabeled Anti-CD8 Minibody","route":"/key-papers/paper-farwell-j-nucl-med/"}],"bottleneck":[{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"idea":[{"id":"idea-tr2-ctdna-futility-gates","kind":"idea","name":"Kill combination arms early using circulating tumour DNA, before waiting for scans","route":"/ideas/idea-tr2-ctdna-futility-gates/"},{"id":"idea-bio2-ctdna-six-week-io-switch","kind":"idea","name":"Use a blood test at six weeks to decide whether to keep going","route":"/ideas/idea-bio2-ctdna-six-week-io-switch/"}]}}