451 CD40L-4–1BB can stimulate tumor infiltrating lymphocyte ex vivo expansion from melanoma core biopsies
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
