CART Cell Cancer Immunotherapy
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Cancer patients’ response to immunotherapy may be predictable in part based on their levels of CD8+ T-cell infiltration, according to a new study. Such drugs are one of the world’s highest selling classes, estimated to have netted over $31B in 2021 and expected to bring almost $150M by 2030. But only 15%-20% of patients respond to them, which makes identifying potential responders particularly important.

Scientists at the University Medical Centre Groningen performed whole-body PET scans using a radioactively labeled antibody tracer against CD8+ T cells, before and thirty days after the start of treatment with immune checkpoint inhibitors. After showing the radioactive tracer binds effectively to CD8+ T cells, the team determined that the presence of those cells can be linked to immunotherapy response in multiple cancers. The results were published in Nature Medicine this week.

“Baseline tumor uptake of [CD8+] tracer showed a positive trend with best overall response evaluation criteria in solid tumors (RECIST) response, and uptake was 40% higher in patients with SD/PR/CR [stable disease, partial response, and complete response] as best overall response,” Liesbeth de Vries, professor of Medical Oncology at the University Medical Centre Groningen, told Inside Precision Medicine. “Moreover, Higher SUVmax [standardized uptake value max] was associated with longer overall survival.”

The immune system can attack tumor cells, but also has ways to silence T cells’ alert against tumors. “Immune checkpoint inhibitors release the full power of T cells on tumors,” said de Vries.

The importance of answering this question, of which patients respond to immunotherapies, is increasing, De Vries tells Inside Precision Medicine, “These drugs are now being used not just as a last resort, but also evaluated to prevent metastasis or to reduce tumor size before an operation,” she noted.

She and a team of scientists at the Medical Center Groningen and others traced CD8+, a marker of activated T-cells, labeled with zirconium-89.

“Activated T cells are everywhere in the entire body, but so far, our knowledge about their distribution was largely based on biopsies. We wanted to study the full picture,” she said.

The team collected tumor biopsies from their patients to confirm the accuracy of the PET scan results. “We compared the amount of radioactivity in the biopsies measured by autoradiography with staining for CD8+ cells. And we found higher tracer uptake in lesions with high CD8+ infiltration,” de Vries said.

But the researchers, “Were stunned by the heterogeneity in response we saw, both within individual patients and between patients,” de Vries said. “It was generally assumed that around 30 days of treatment there would be a clear-cut difference between responders and non-responders in CD8+ T cell presence.” But instead, the response was much more dynamic, with a large spatial and temporal variation in the presence of tumor lesions of activated T cells.

De Vries’ group has plans to advance the research. “We are currently expanding our work for CD8, in a specific tumor type, and for specific treatment, and also with applying other CD8 tracers. For example, when you use a tracer with a radionuclide with a shorter half-life, you may be able to perform repeat imaging at several different time points and thus know more precisely if and when the CD8 response occurs, which might influence treatment decisions in the future,” she said.

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