HER2 specific adoptive T cells shown to localize and infiltrate all sites of disease using combined SPECT and PET imaging.

Sasha E. Stanton, Janet Eary, Edmond Marzbani, David Mankoff, Lupe Salazar, Doreen Higgins, Jessica Reichow, Yushe Dang, Mary L. Disis
Description / Abstract: 

Adoptive T cell therapy has been shown to stimulate anti-tumor response in multiple cancers, however these responses have
not been robust or durable. In previous studies, indium-111 labeled T cells have functioned normally but were either not present
at all sites of metastatic disease or not able to infiltrate the sites of disease. In breast cancer, adoptive HER2 targeted T cells
were unable to penetrate visceral metastases. Previous work in our laboratory has demonstrated that HER2 vaccine-primed
autologous adoptive T cells were safe and well tolerated. In this phase I study, HER2 positive breast cancer patients received
three HER2 peptide vaccines before plasmapheresis and ex-vivo expansion of HER2 specific autologous T cells to evaluate the
immune and clinical response to adoptive T cell therapy in breast cancer. In one patient, the trafficking of indium-111 labeled T
cells was also evaluated using SPECT and PET imaging.
An aliquot of 1X107 expanded T cells were labeled with 300 uCi of indium-111 and given with the third T cell infusion. Prior in
vitro studies had demonstrated that labeled HER2 expanded T had similar viability (at 24 hours 97±1% viability with unlabeled
cells and 90.9±1.1% viability with 480 uCI labeled cells) and interferon gamma release (263±8 pg/mL released in unlabeled cells
and 208.5±11 released in 480 uCi labeled cells) as unlabeled HER2 expanded T cells when stimulated by IL2. SPECT imaging
demonstrated that the T cells trafficked to all the metastatic sites of disease by 24 hours and completely infiltrated the tumor.
The patient studied had metastases to her skull, left axilla, sternum, bilateral proximal humeri, and sacrum. The corrected
indium-111 uptake at 24 hours varied from 2.27 counts per pixel in the R proximal humerus to 6.28 counts per pixel in the R
sacrum and remained elevated at 48 hours (for example a continued 6.9 counts/pixel signal at the R sacrum). Concurrent PET
CT imaging demonstrated FDG flare at 48 hours at all sites of metastatic disease including a 1.3 fold increase in the R proximal
humerus and a 1.3 fold increase in the L proximal humerus signal over baseline scans. This increased FDG uptake had
resolved 1 month after therapy. After this study, the patient had stable disease for 18 months. She had a robust response to
each T cell infusion and the booster vaccines, including fevers, headaches, and increased pain at the sites of metastatic
disease. These symptoms have been associated with a disease specific T cell response. This study demonstrates by a novel
method of concurrent SPECT and PET imaging that the ex-vivo expanded HER2 specific T cells were able to traffic to and fully
infiltrate all sites of metastatic disease causing an acute FDG-PET flare and prolonged stable disease in a HER2 positive breast
cancer patient with bone-only metastatic disease. Further studies are now needed to confirm if this imaging method can be used
universally in adoptive T cell studies.

Other ID: 
Control/Tracking Number: 15-A-1371-AACR