Table 2.
Infusion products and clinical responses
| Patient nr | TIL characteristics | Phenotype | Reactivity against autologous tumor | Clinical results | |||||||||||||
| *cells (x1010) | Culture time | % CD8+ | % CD4+ | % PD1+ | % CCR7+ | % CD27+ | % CD28+ | % CD45RA+ | % CD62L+ | % IFN-γ | % TNF-α | % IL-2 | # IL-2 | Result | Survival | ||
| Pre-REP TIL | Of total CD8+ or CD4+* | Infusions | |||||||||||||||
| No clinical benefit | |||||||||||||||||
| 1 | 12.0 | 21 | 91.1 | CD8+ | 22.4 | 3.9 | 5.1 | 45.7 | 8.6 | 3.9 | 0,19† | nd | nd | 9 | PD | 17 mo | |
| 1.3 | CD4+ | 19.7 | 8.4 | 5.5 | 1.8 | 17.9 | 8.4 | nd | nd | nd | |||||||
| 2 | 9.8 | 18 | 32.1 | CD8+ | 26.4 | 2.1 | 1.4 | 50.5 | 10.9 | 22.5 | 14.2 | 5.2 | 1.1 | 3 | SD (2 mo) | 7 mo | |
| 64.1 | CD4+ | 30.6 | 2.9 | 2.2 | 1.2 | 2.2 | 14.4 | 1.4 | 6.2 | 0.2 | |||||||
| 6 | 15.0 | 14 | 69.0 | CD8+ | 23.7 | 2.2 | 2.0 | 55.2 | 4.2 | 13.8 | 1.6 | 0.4 | 0.2 | 4 | PD | 2 mo | |
| 19.6 | CD4+ | 11.8 | 2.1 | 2.6 | 3.2 | 4.8 | 4.6 | 2.1 | 0.5 | 0.8 | |||||||
| 9 | 14.9 | 19 | 94.9 | CD8+ | 13.0 | 1.4 | 2.3 | 32.9 | 2.2 | 3.7 | 10.8 | 0.7 | 0.5 | 2 | PD | 2 mo | |
| 3.0 | CD4+ | 13.7 | 5.9 | 5.7 | 2.1 | 8.2 | 7.9 | 4.0 | 5.5 | 0.0 | |||||||
| 10 | 1.7 | 15 | 37.6 | CD8+ | 64.9 | 5.5 | 2.9 | 26.1 | 96.5 | 1.4 | 5.8 | 0.9 | 0.4 | 6 | PD | 1.5 mo | |
| 55.9 | CD4+ | 56.1 | 4.1 | 4.2 | 0.7 | 98.3 | 1.3 | 13.0 | 23.2 | 7.7 | |||||||
| Clinical benefits | |||||||||||||||||
| 3 | 19.6 | 18 | 79.4 | CD8+ | 47.8 | 4.7 | 4.6 | 43.5 | 2.4 | 7.1 | 19.4 | nd | nd | 4 | CR (108 mo+) |
108 mo+ | |
| 6.2 | CD4+ | 23.2 | 5.6 | 6.5 | 3.2 | 6.8 | 7.2 | nd | nd | nd | |||||||
| 4 | 7.0 | 18 | 25.4 | CD8+ | 6.6 | 4.1 | 3.6 | 50.0 | 7.4 | 21.7 | 4.1 | 3.3 | 0.9 | 2 | PR (6 mo) | 16 mo | |
| 57.0 | CD4+ | 7.8 | 5.3 | 3.5 | 1.7 | 4.3 | 14.6 | 1.7 | 2.5 | 1.4 | |||||||
| 5 | 18.9 | 17 | 95.8 | CD8+ | 2.8 | 1.4 | 2.7 | 5.5 | 0.4 | 0.5 | 9.5 | nd | nd | 2 | PR (6 mo) | 24 mo | |
| 1.0 | CD4+ | 20.5 | 7.5 | 6.8 | 2.5 | 1.9 | 3.1 | nd | nd | nd | |||||||
| 7 | 13.9 | 16 | 81.4 | CD8+ | 6.9 | 12.3 | 7.4 | 49.7 | 57.4 | 50.4 | 0.3 | 0.0 | 0.0 | 4 | PR (5 mo) | 42 mo | |
| 10.4 | CD4+ | 5.79 | 8.15 | 7.42 | 7.22 | 20.27 | 38.47 | 0.1 | 2.2 | 0.2 | |||||||
| 8 | 14.7 | 11 | 60.4 | CD8+ | 13.3 | 9.5 | 15.3 | 21.2 | 21.5 | 5.0 | 14.3 | 8.5 | 3.7 | 1 | CR (84 mo+) |
84 mo+ | |
| 19.3 | CD4+ | 11.6 | 7.0 | 13.9 | 1.4 | 12.5 | 3.8 | 1.4 | 1.0 | 0.1 | |||||||
*Background levels of cytokine production by T cells cultured without tumor material was subtracted.
†No autologous tumor line or digest available. Reactivity of infusion TIL tested against partly HLA matched melanoma cell line nd=not determined.
CR, complete remissions; IFN-γ, interferon-γ; mo, month; PR, partial response; TIL, tumor infiltrating lymphocyte; TNF-α, tumor necrosis factor α.