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294 CD8 PET imaging of tumor infiltrating T cells in advanced solid tumors: a phase I first-in-human study of 89Zr-IAB22M2C, a radiolabeled anti-CD8 minibody
  1. Michael Farwell1,
  2. Raymond Gamache1,
  3. Neeta Pandit-Taskar2,
  4. Mike Postow2,
  5. Michael Gordon3,
  6. Ian Wilson4,
  7. Alessandro Mascioni4,
  8. Anna Wu5,
  9. William Le4,
  10. Avital Weiss4 and
  11. Ronald Korn4
  1. 1University of Pennsylvania, Philadelphia, PA, USA
  2. 2Memorial Sloan Kettering Cancer Center, New York, NY, USA
  3. 3HonorHealth Research Institute, Scottsdale, AZ, USA
  4. 4ImaginAb, Ingelwood, CA, USA
  5. 5City of Hope, Duarte, CA, USA


Background Tumor infiltration by CD8 T cells is associated with favorable outcomes to immunotherapy (IOT). However, biopsies to assess T cell infiltration are invasive and prone to sampling error. CD8 PET imaging could provide an effective non-invasive method of visualizing T cell trafficking and tumor infiltration and predicting early response to IOT.

Methods A phase 1 first-in-human PET imaging study using an anti-CD8 radiolabeled Minibody, 89Zr-IAB22M2C (CD8-tracer), to detect whole body and tumor CD8 distribution in patients with metastatic solid tumors was completed. Patients received 3 mCi 89Zr-IAB22M2C followed by serial PET scans over a 5–7-day period. A two-stage design included protein dose escalation phase1 (n=6, 0.2 mg to 10 mg API) to establish safety and optimal scanning parameters and a dose expansion phase focusing on two API doses (0.5 mg (n=4) or 1.5 mg (n=5) API). All patients were monitored for drug-related adverse events with blood chemistry, hematology, cytokine assay and anti-drug antibodies (ADA). Biodistribution, radiodosimetry and SUV PET uptake was performed in all patients.

Results 15 subjects (31–82 years, M/F = 9/6) with metastatic melanoma (n=8), NSCLC (n=6), and HCC (n=1) were enrolled. Treatment histories included naïve (n=2), discontinued prior IOT (n=3), active IOT (n=10). No drug-related AEs nor abnormal laboratory tests were noted except for a transient increase in ADA in 1 subject. The CD8-tracer accumulated in tumors and CD8 rich tissues (e.g. spleen, marrow, nodes) with maximum uptake at 24–48 hours post injection along with low background activity in non-T cell rich tissues (e.g. muscle, heart). More favorable dosimetry was seen at 1.5 mg versus 0.5 mg API (effective dose=0.64 mSv/MBq versus 0.67 mSv/MBq, respectively). Comparison of 1.5 mg and 0.5 mg API in expansion cohorts demonstrated similar uptake in nodes but with reduced uptake in marrow and spleen at the higher API. Tracer-uptake in tumors was noted in 10/15 (67%) subjects, favoring slightly higher tumor uptake in the 1.5 mg cohort. One patient with advanced melanoma on IOT had increased CD8-tracer uptake in several metastases on an early post treatment scan, which correlated with response (figure 1).

Abstract 294 Figure 1

71 year old man with locally advanced stage III melanomaFDG PET/CT imaging (left) shows two FDG avid metastases in the left axilla. CD8 PET/CT imaging (middle) performed 28 days after starting immunotherapy demonstrates increased tracer activity in both metastases, suggestive of tumor infiltration by CD8 T cells. Follow-up imaging via CT (right) confirmed a complete response to therapy.

Conclusions 89Zr-IAB22M2C targets CD8+ rich tissues and visualizes whole-body biodistribution of CD8+ cells in tumors and reference tissues and may predict early response to IOT. A 1.5 mg protein dose provides similar distribution to 0.5 mg dose, with more favorable dosimetry and is used in the ongoing Phase 2 study.

Acknowledgements None

Trial Registration ClinicalTrials. gov Identifier: NCT03107663

Ethics Approval The study was approved by Institutional Review Boards of MSKCC (IRB #16-1109), Honor Health (West IRB #1179278) and University of Pennsylvania (IRB # 828992).

Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.


  1. Michael S. Gordon, MD et al, November 2018, Imaging of tumor infiltrating T cells with an anti-CD8 minibody 89Zr-IAB22M2C in advanced solid tumors: a phase I first-in-human study, presented at 33th Annual SITC meeting (session O48).

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