Ex Vivo Expanded Multi-Antigen Specific Lymphocytes for the Treatment of Solid Tumors

3042 Background: Patients with solid tumors refractory to standard therapies have poor prognoses, and most salvage therapies are toxic and ineffective. Antigen-specific T cell therapies offer a promising alternative for targeted therapy with the ability to target multiple antigens in a single product. Hence, we hypothesize that patient-derived tumor-associated antigen-specific T cells (TAA-T) targeting WT1, PRAME, and survivin expressed by pediatric solid tumors can be safely administered to treat patients with relapsed/refractory disease. The objective of this phase I clinical trial is to determine the safety of administering TAA-T to these patients. The secondary objectives include determining disease response and tumor-specific immune reconstitution following infusion. Methods: T cells expanded from patient peripheral blood were stimulated weekly with antigen presenting cells pulsed with an overlapping peptide library spanning the TAAs WT1, PRAME, and survivin. Following release testing, patients were infused with TAA-T on a dose escalation study, ranging from 1 x 107/m2 (dose level 1) to 4 x 107/m2 (dose level 3). Clinical and immune studies were performed post-infusion to monitor for adverse effects and assess immune and disease responses. Results: We have generated TAA-T products from 14 patients (age range 6-54 years) with relapsed/refractory solid tumors (neuroblastoma, osteosarcoma, Wilms tumor, Ewing sarcoma, soft tissue sarcoma, rhabdomyosarcoma). 14 patients have received a median of 2 (range 1-8) infusions without product-related SAEs post-infusion. Epitope spreading was identified in 86% of responding patients. Preliminary outcome data (N = 10) show overall survival of 82% and event-free survival of 54% at 3 months. Conclusions: This unique immunotherapeutic has been well tolerated without causing life-threatening adverse events. Despite aggressive and multiply relapsed disease, 75% of patients have demonstrated evidence of disease control after TAA-T with epitope spreading identified in the majority of responding patients post-infusion. These clinical and laboratory data suggest that TAA-T may safely prolong survival in patients with relapsed/refractory solid tumors. Clinical trial information: NCT02789228.