Phase I clinical trial with a human major histocompatibility complex nonrestricted cytotoxic T-cell line (TALL-104) in dogs with advanced tumors.
The human TALL-104 cell line is endowed with a uniquely potent MHC nonrestricted tumoricidal activity across several species. In view of the potential applicability of TALL-104 cells as an anticancer agent, this study was conducted to evaluate the possible toxicity and efficacy of this new cell therapy in a superior animal model with spontaneous tumors. Nineteen canine cases with advanced, refractory malignancies of various histological types were entered in the study. All dogs had failed all other available treatments and had very limited life expectancy. Cyclosporin A was administered p.o. (10 mg/kg/day) starting from the day before TALL-104 cell administration throughout the treatment to prevent rejection of the xenogeneic effectors. Lethally irradiated (40 Gy) TALL-104 cells (10(8)/kg) were administered systemically following two treatment schedules. In the first schedule, the cells were given every other day for 2 weeks in a row and then once a week for 3 additional weeks; in the second schedule, TALL-104 cells were administered daily for a total of 5 days. None of the 19 cases showed significant clinical or laboratory toxicity; in addition, none of the dogs had to be withdrawn from the study because of immediate adverse reactions to the infusions. The severe side effects usually associated with classical lymphokine-activated killer therapy in association with high doses of interleukin 2, such as "capillary leak syndrome," were absent in this study. Remarkably, TALL-104 therapy induced various degrees of antitumor effects in 7 of the 19 dogs, including 1 complete response (continuing at +13 months), three partial responses (duration of 2 months, 3 months, and continuing at +2 months), and three transient responses. Clinical responses and immunological parameters correlated well in each case. Taken together, these data indicate that systemic administration of lethally irradiated TALL-104 cells in the absence of exogenous interleukin 2 may be regarded as a safe and promising adjuvant type of treatment for advanced cancer patients.
Cesano
A
A
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Visonneau
S
S
Jeglum
K A
KA
Owen
J
J
Wilkinson
K
K
Carner
K
K
Reese
L
L
Santoli
D
D
D000818:Animals; D004283:Dog Diseases / Q000628:therapy*; D004285:Dogs; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D009369:Neoplasms / Q000276:immunology / Q000628:therapy / Q000662:veterinary*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*