Background: Sip-T is an FDA-approved autologous cellular immunotherapy for asymptomatic or minimally symptomatic mCRPC. Neoadjuvant sip-T induced activated T-cell infiltration to the prostate tissue (Fong 2014) and broadened the T cell receptor (TCR) repertoire vs control (Sheikh 2016). To test if sip-T induces memory T-cell responses, we compared treatment-induced changes in TCR repertoire of treatment-naïve pts (STRIDE) with those retreated with sip-T (P10-1). Methods: In STRIDE (N=52), pts received sip-T with concurrent or sequential enzalutamide (Petrylak 2015). In P10-1 (N=8), pts previously treated with sip-T in an androgen-dependent setting were retreated with a booster course after a median of 8.6 years (Beer 2013). PBMCs were collected at baseline and during/post–sip-T. Deep sequencing was performed using the ImmunoSEQ assay (Adaptive Biotechnologies). TCR diversity was assessed by Shannon diversity index and clonality. TCR dynamics was evaluated by Morisita’s distance (Zhang 2017). Results: Baseline TCR diversity was similar between the two trials (p=0.590, Shannon diversity index; p=0.700, clonality). Significant decreases in clonality were observed from baseline to wk 4 (p<0.001) and wk 6 (p=0.030) in STRIDE, but not in P10-1, indicating more expansion of T cell clones in STRIDE. Morisita’s distance was significantly higher at wk 2 (p=0.040) and 26 (p=0.013) in STRIDE vs P10-1, indicating a more consistent TCR repertoire in STRIDE across timepoints. The proportion of the clones enriched after sip-T treatment was significantly higher in P10-1 vs STRIDE (wk 6: p=0.007, wk 26: p=0.015, wk 52: p=0.026). The extent of change within the top 100 most abundant TCR sequences (clonal shuffling) was greater and initiated earlier in P10-1 vs STRIDE. Conclusions: Initial sip-T treatment of naïve mCRPC pts programs the TCR repertoire, which is maintained over time. Consistent with immunologic memory, retreatment with sip-T rapidly expands the number of enriched T-cell clones persisting up to 1 year after retreatment, which is characteristic of immunological boosting following successful treatment.