Immunotherapy With a Tumor-Infiltrating Lymphocyte Clone, Soluble Antigen, and Cyclophosphamide

Hirotaka Komichi, MD, PhD; Scott Smith; Barry D. Kahan, MD, PhD
Arch Surg. 1992;127(12):1417-1423. doi:10.1001/archsurg.1992.01420120051009.
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• A tumor-specific cytotoxic T-lymphocyte clone derived from bulk cultures of tumor-infiltrating lymphocytes attenuated the outgrowth of methylcholanthrene (MCA)—induced fibrosarcomas in C3H/HeJ mice. In 4-hour chromium 51–release assays, bulk cultures of tumor-infiltrating lymphocytes showed nonspecificity for MCA-induced tumors (MCA-F, MCA-D, MCA-SP), YAC-1, and EL-4. In contrast, a cytotoxic T-lymphocyte—cloned line specifically killed MCA-F, but not MCA-D or MCA-SP. Cytotoxic T-lymphocyte line 8 protected syngeneic hosts in local and systemic adoptive transfer assays. Hosts bearing 4-day-established MCA-F tumor cells received single agents or combinations of isoelectrophoretically purified butyl alcohol—extracted tumor-specific transplantation antigen (1 μg/wk), cyclophosphamide (20 mg/kg on days 4 and 11), and/or cytotoxic T-lymphocytes (1 × 107 cells on days 7 and 14). While the mean tumor diameter was 11.6±1.3 mm in untreated hosts or after single treatments, the combination of tumor-specific transplantation antigen and cyclophosphamide along with the cytotoxic T-lymphocyte clone resulted in tumor diameters of 1.8±0.5 mm. The triple combination prolonged host survival from 39.6±1.6 to 57.2±4.7 days compared with antigen and cyclophosphamide treatment.

(Arch Surg. 1992;127:1417-1423)


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