Background Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) represents a promising strategy for the treatment of patients with advanced melanoma (MEL). In this study we performed a pooled analysis of efficacy outcomes of TIL in advanced MEL patients treated at Moffitt Cancer Center. Methods Data were extracted from 4 phase 1/2 clinical trials of MEL patients treated with TIL only, TIL with ipilimumab (ipi), TIL with nivolumab (nivo), and TIL with vemurafenib (vem). Progression-free survival (PFS) and overall-survival (OS) were assessed in both intention-to- treat [ITT] and TIL-treated [TT] patients. Clinical and TIL infusion product characteristics in relation to objective response rate (ORR) and PFS were analyzed in the TT population. Results From 2009–2018 60 MEL patients, 25 female (42%) and 35 male (58%), median age= 49 [IQR, 41–56], were enrolled in TIL only (n=19, 32%), TIL with ipi (n=13, 22%), TIL with nivo (n=11, 18%), and TIL with vem (n=17, 28%) trials.

Background Tumor-infiltrating lymphocyte (TIL) expansion ex vivo is currently performed from surgically excised tumors in culture media containing Interleukin-2 (IL-2). Targeting antigen-presenting cells through CD40 and tumor-reactive T cells through 4-1BB signaling may result in more robust anti-tumor activity. In this study we investigated the impact of coordinated CD40L and 4-1BB costimulation on ex vivo TIL expansion from melanoma core needle biopsies (CNB). Methods As part of an IRB approved protocol, additional CNB passes were obtained from melanoma patients utilizing ultrasound- or CT-guidance with 18- or 20-gauge needles as part of their clinical care. Each core was plated individually in a G-Rex 24 well plate in 8 mL of culture media containing IL-2 (6000 IU/mL) and bispecific CD40L/4-1BBL fusion protein (43nM) with additional IL-2 on days 7, 14, 21. Resulting TIL were harvested on day 28. Flow cytometry was performed on TIL and tumor-reactivity was measured with HLA-matched

Background Tumor-infiltrating lymphocyte (TIL) expansion ex vivo is currently performed from surgically excised tumors in culture media containing Interleukin-2 (IL-2). Targeting antigen-presenting cells through CD40 and tumor-reactive T cells through 4-1BB signaling may result in more robust anti-tumor activity. In this study we investigated the impact of coordinated CD40L and 4-1BB costimulation on ex vivo TIL expansion from melanoma core needle biopsies (CNB). Methods As part of an IRB approved protocol, additional CNB passes were obtained from melanoma patients utilizing ultrasound- or CT-guidance with 18- or 20-gauge needles as part of their clinical care. Each core was plated individually in a G-Rex 24 well plate in 8 mL of culture media containing IL-2 (6000 IU/mL) and bispecific CD40L/4-1BBL fusion protein (43nM) with additional IL-2 on days 7, 14, 21. Resulting TIL were harvested on day 28. Flow cytometry was performed on TIL and tumor-reactivity was measured with HLA-matched

Background Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) represents a promising strategy for the treatment of patients with advanced melanoma (MEL). In this study we performed a pooled analysis of efficacy outcomes of TIL in advanced MEL patients treated at Moffitt Cancer Center. Methods Data were extracted from 4 phase 1/2 clinical trials of MEL patients treated with TIL only, TIL with ipilimumab (ipi), TIL with nivolumab (nivo), and TIL with vemurafenib (vem). Progression-free survival (PFS) and overall-survival (OS) were assessed in both intention-to- treat [ITT] and TIL-treated [TT] patients. Clinical and TIL infusion product characteristics in relation to objective response rate (ORR) and PFS were analyzed in the TT population. Results From 2009–2018 60 MEL patients, 25 female (42%) and 35 male (58%), median age= 49 [IQR, 41–56], were enrolled in TIL only (n=19, 32%), TIL with ipi (n=13, 22%), TIL with nivo (n=11, 18%), and TIL with vem (n=17, 28%) trials.