title: Phase I trial of TALL-104 cells in patients with refractory metastatic breast cancer.
abstract: The human cytotoxic T-cell line TALL-104 displays antitumor effects in animals with implanted and spontaneous malignancies. A Phase I trial was conducted to determine toxicity of TALL-104 cell therapy in women with metastatic refractory breast cancer. Fifteen patients with metastatic infiltrating ductal (n = 12), lobular (n = 2), or medullary (n = 1) carcinoma received escalating doses of lethally irradiated TALL-104 cells (three patients/group received 10(6), 3 x 10(6), 10(7), 3 x 10(7), and 10(8) cells/kg) for 5 consecutive days (induction course). Patients without progressive disease received 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 10(8) cells/kg, 3 weeks after the induction course. Nine patients progressed within 1 month from induction, and five 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 relief 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 induction 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 preliminary trial demonstrate that further investigation of TALL-104 cell therapy is warranted.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: S
authors.initials: S
authors.lastname: Visonneau
authors.forename: A
authors.initials: A
authors.lastname: Cesano
authors.forename: D L
authors.initials: DL
authors.lastname: Porter
authors.forename: S L
authors.initials: SL
authors.lastname: Luger
authors.forename: L
authors.initials: L
authors.lastname: Schuchter
authors.forename: M
authors.initials: M
authors.lastname: Kamoun
authors.forename: M H
authors.initials: MH
authors.lastname: Torosian
authors.forename: K
authors.initials: K
authors.lastname: Duffy
authors.forename: C
authors.initials: C
authors.lastname: Sickles
authors.forename: E A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: D
authors.initials: D
authors.lastname: Santoli
mesh_terms: D000328:Adult; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002455:Cell Division; D002460:Cell Line; D016207:Cytokines / Q000097:blood; D003602:Cytotoxicity, Immunologic; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D015375:Receptors, Interleukin-2 / Q000097:blood; D012871:Skin Diseases / Q000139:chemically induced; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D016207:Cytokines; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1