Phase I trial of TALL-104 cells in patients with refractory metastatic breast cancer

The human cytotoxic T-cell line TALL-104 displays antitumor effects in anim als with implanted and spontaneous malignancies. A Phase I trial was conduc ted to determine toxicity of TALL-104 cell therapy in women with metastatic refractory breast cancer. Fifteen patients with metastatic infiltrating du ctal (n = 12), lobular (n = 2), or medullary (n = 1) carcinoma received esc alating doses of lethally irradiated TALL-104 cells (three patients/group r eceived 10(6), 3 x 10(6), 10(7), 3 x 10(7), and 10(8) cells/kg) for 5 conse cutive days (induction course), Patients without progressive disease receiv ed monthly maintenance 2-day infusions at the same dose level, Mild grade I /II toxicity developed in 11 patients regardless of cell dose, One grade IV toxicity consequent to hepatic tumor necrosis occurred in a patient given 108 cells/kg, 3 weeks after the induction course, Nine patients progressed within 1 month from induction, and fire patients had stable disease for 2-6 months, One patient (at 3 x 10(7)/kg) had improvement of liver metastases and ascites. and a second patient (at 10(6)/kg) experienced a dramatic reli ef in bone pain. Increases in blood natural killer cell activity and levels of IFN-gamma, interleukin-10, and activation markers (soluble interleukin- 2 receptor and soluble intercellular adhesion molecule-1) were often seen. Only one patient developed anti-HLA class I antibody responses against TALL -104 cells; specific CTL activity developed in three patients during induct ion and in four patients during the maintenance boosts. In conclusion, TALL -104 cells were well tolerated by patients with metastatic breast cancer at the doses and regimen tested. The clinical responses observed in this prel iminary trial demonstrate that further investigation of TALL-104 cell thera py is warranted.