Abstract 649: Emigrant pre-REP tumor infiltrating lymphocytes profoundly differ from remnant T-cells

Adoptive T cell therapy with autologous tumor infiltrating lymphocytes (TIL) provides up to 56% objective response rates and a complete response in 24% of patients with metastatic melanoma. The process of generating TIL from resected tumor involves morcellating the tumor into 1-3 mm3 fragments and expanding TIL in the presence of Interleukin 2 (IL-2) in a pre-Rapid Expansion Protocol (pre-REP). During the ‘pre-REP’, tumor-resident immune cells emigrate (eTIL) and proliferate. The length of the pre-REP varies between 11-21 days, depending on cell growth. Residual tumor fragments (remnants) are discarded and the expanded eTIL are subjected to a Rapid Expansion Protocol (REP) with irradiated PBMC feeders, anti-CD3 and IL-2. Viable cells remaining in the tumor remnants (rTIL) following the pre-REP were investigated to assess their function and phenotype. We evaluated and compared the rTIL and eTIL in melanoma, breast, renal, pancreatic, lung and colorectal tumors (n=9). Tumor rTIL are consistently phenotypically distinct from eTIL, as determined by differential expression of various markers (Table 1). The fundamental differences in rTIL were: Increased CD69+ (7 fold MFI in CD4+) (p