Adoptive T cell therapy using antigen-specific CD8⁺T cell clones for the treatment of patients with metastatic melanoma:In vivopersistence, migration, and antitumor effect of transferred T cells

Adoptive T cell therapy, involving theex vivoselection and expansion of antigen-specific T cell clones, provides a means of augmenting antigen-specific immunity without thein vivoconstraints that can accompany vaccine-based strategies. A phase I study was performed to evaluate the safety,in vivopersistence, and efficacy of adoptively transferred CD8⁺T cell clones targeting the tumor-associated antigens, MART1/MelanA and gp100 for the treatment of patients with metastatic melanoma. Four infusions of autologous T cell clones were administered, the first without IL-2 and subsequent infusions with low-dose IL-2 (at 0.25, 0.50, and 1.0 × 10⁶units/m²twice daily for the second, third, and fourth infusions, respectively). Forty-three infusions of MART1/MelanA-specific or gp100-specific CD8⁺T cell clones were administered to 10 patients. No serious toxicity was observed. We demonstrate that the adoptively transferred T cell clones persistin vivoin response to low-dose IL-2, preferentially localize to tumor sites and mediate an antigen-specific immune response characterized by the elimination of antigen-positive tumor cells, regression of individual metastases, and minor, mixed or stable responses in 8 of 10 patients with refractory, metastatic disease for up to 21 mo.