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

TLDR

Adoptive T cell therapy expands antigen‑specific T cell clones ex vivo to enhance immunity without the in vivo limitations of vaccines. This phase I study assessed the safety, persistence, and antitumor efficacy of CD8⁺ T cell clones targeting MART1/MelanA and gp100 in patients with metastatic melanoma. Patients received four infusions of autologous CD8⁺ T cell clones—initially without IL‑2, then with escalating low‑dose IL‑2—totaling 43 infusions across 10 patients. No serious toxicity occurred, and the transferred clones persisted, homed to tumors, eliminated antigen‑positive cells, regressed metastases, and yielded minor, mixed, or stable responses in 8 of 10 patients for up to 21 months.

Abstract

Adoptive T cell therapy, involving the ex vivo selection and expansion of antigen-specific T cell clones, provides a means of augmenting antigen-specific immunity without the in vivo constraints that can accompany vaccine-based strategies. A phase I study was performed to evaluate the safety, in vivo persistence, 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 × 10 6 units/m 2 twice 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 persist in vivo in 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.