Abstract 2937: Localization of sipuleucel-T- expanded T cell clones into tumors of treated prostate cancer patients
Authors: Lawrence Fong, Todd DeVries, Jason Cham, Li Zhang, Mark Frohlich, James Trager, Nadeem Sheikh
Journal: Cancer Research (2014)

Abstract Sipuleucel-T is an FDA-approved autologous cellular therapy demonstrated to prolong overall survival in subjects with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC). Sipuleucel-T is generated by culturing patients' own peripheral blood mononuclear cells (PBMC) with a fusion protein of prostatic acid phosphatase and granulocyte macrophage colony stimulating factor. While antigen presenting cells take up this antigen and can prime antigen specific T cells in vivo, the majority of the cells in the sipuleucel-T product are in fact T cells. Moreover, antigen-specific T cells in the product become activated during production of sipuleucel-T, particularly for the 2nd and 3rd infusions. To examine whether T cells contained in sipuleucel-T might be homing to the site of the tumor, we used a next-generation sequencing-based method to assess T cell repertoire diversity in the blood, sipuleucel-T product, and resected tissues of patients participating in a neoadjuvant study of sipuleucel-T treatment (P07-1; NCT00715104). In this trial, patients with localized prostate cancer received sipuleucel-T prior to undergoing radical prostatectomy (RP). DNA extracted from the different samples was amplified using a multiplex PCR assay to amplify the CDR3 region of the T cell receptor spanning the variable region formed by the junction of the V, D and J segments and their associated non-templated insertions. Sequence reads were used to quantitate absolute TCR frequencies using standardized clonotype determination algorithms. We found that a subset of T cell clones was enriched in the generation of sipuleucel-T. We also found that T cell clones were expanded in patient blood after each successive infusion. When we examined the T cell clonotypes in the prostate tissues resected after sipuleucel-T treatment, we found that there were T cell clones in the prostate in common with the sipuleucel-T product. Interestingly a number of the clones present in the pre-treatment blood were reduced or lost in the blood by the second and third infusion but were present in the post-treatment prostate tissue, consistent with trafficking of the T cell clones from the peripheral circulation. These results indicate that ex vivo production of sipuleucel-T induces the expansion of certain T cell clones that are ultimately present in the prostates of patients treated prior to RP. Sipuleucel-T may therefore also function as an adoptive T cell therapy. Citation Format: Lawrence Fong, Todd DeVries, Jason Cham, Li Zhang, Mark Frohlich, James Trager, Nadeem Sheikh. Localization of sipuleucel-T- expanded T cell clones into tumors of treated prostate cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2937. doi:10.1158/1538-7445.AM2014-2937