Adjuvant Treatment of Canine Osteosarcoma with the Human Cytotoxic T-Cell Line TALL-104

Adjuvant Treatment of Canine Osteosarcoma with the Human Cytotoxic T-Cell Line TALL-1041

The Wistar Institute, Philadelphia, Pennsylvania 19104 [ S. V., A. C., D. S.], and Veterinary Oncology Services and Research Center, West Chester, Pennsylvania 19380 [K. A. J.]

Abstract

The human cytotoxic T-cell line TALL-104 has been used successfully to treat cancer in experimental mouse models with implanted tumors and in dogs with spontaneously occurring malignancies. This study investigated the efficacy of TALL-104 cells given in an adjuvant setting to dogs with appendicular osteosarcoma after surgery and chemotherapy. Of the 23 dogs enrolled in the study, 20 had undergone amputation of the affected limb, and 3 had undergone limb salvage surgery. After surgery, all dogs but one received cisplatin (CDDP) chemotherapy (60 mg/m² i.v. every 21 days × 1–4 cycles). Four dogs also received one to six cycles of CDDP before limb amputation. After CDDP therapy, dogs without overt metastasis received γ-irradiated (40 Gy) TALL-104 cells systemically (10⁸/kg) for 5 consecutive days, followed by 2-day monthly boosts (at the same dose) for a total of 9 months. Of the 23 dogs treated, 9 survive disease-free at 12.1–29.5 months after surgery, 11 died of metastatic disease between 5 and 21.5 months, 1 experienced a relapse in the lung 9.5 months after surgery but is still alive without further treatment at 13 months, 1 developed severe discopathy at 4 months after surgery, and 1 developed progressive neuropathy at 5.9 months after surgery. The overall median survival time is 11.5 months, and the median disease-free interval is 9.8 months. Our cell therapy results compare favorably with historical median survival times (up to 9 months) and disease-free intervals (up to 7.5 months) of dogs with osteosarcoma receiving standard therapy (surgery and chemotherapy) and support the effectiveness of adjuvant TALL-104 cell administration in preventing or delaying disease recurrence in these dogs.

Footnotes

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↵1 Supported by American Cancer Society Grant RPG-91-018-06-CIM and NIH Core Grant CA-10815.
↵2 S. V. and A. C. contributed equally to this work.
↵3 To whom requests for reprints should be addressed, at The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104. Phone: (215) 898-3978; Fax: (215) 573-7919; E-mail: santoli{at}wistar.upenn.edu
↵4 The abbreviations used are: ST, survival time; DFI, disease-free interval; PBMC, peripheral blood mononuclear cell; NK, natural killer; TNF, tumor necrosis factor; GM-CSF, granulocyte macrophage colony-stimulating factor; GI, gastrointestinal; CDDP, cisplatin; IL, interleukin.
- Accepted March 28, 1999.
- Received November 16, 1998.
- Revision received February 22, 1999.