trials with very small patient populations, individual responses have been seen 
in other malignancies including Hodgkins and non-Hodgkins lymphomas and lung cancer. 
The advantage of LAK cells is the ease of preparation from peripheral blood mononuclear 
cells (PMBC) and the subsequent culture in media with comparatively high doses of rlL- 
2. However, in trafficking studies 4 using cells labelled with Indium 111 , these cells have 
not demonstrated a targeting to the tumor suggesting that LAK cells promote tumor 
reduction by a systemic and anti-tumor effect. 
Cells that infiltrate tumors can be a potential source of cytotoxic anti-tumor effector 
lymphocytes. Belldegrun et al 5 demonstrated that the predominant Tumor- Infiltrating 
Lymphocyte (TIL) population in renal cell carcinoma is composed of CD8-(+)/CD3(+) 
cytotoxic T-cells and other CD8(+)/T-cells. Renal cell TIL can expand significantly with 
comparatively small doses of rIL-2. No significant differences in phenotype were 
identified between tumor derived CD8(+) T cells and peripheral blood CD8(+) T-cells. 
Barth et al 6 , recently reported that TIL from four antigenically distinct tumors cultured 
with low doses of rIL-2 were found to retain their specificity for over three months in 
culture. TIL with m vitro specificity were therapeutically effective in eliminating 
established micrometastases in murine models. Also, using the combination of 
cyclophosphamide, TIL and rIL-2, all of the mice bearing transplantable murine 
adenocarcinoma were cured of advanced hepatic pulmonary metastases and 50 percent 
were cured of advanced pulmonary metastases without notable toxicity. 
An initial study 7 utilizing rIL-2 and TIL demonstrated a partial response with renal cell 
carcinoma in four study subjects treated and one partial response of six study subjects 
treated for melanoma. Major clinical responses have been noted when using rIL-2 and 
expanded TIL in the treatment of melanoma in an on-going trial at the NCI 8 . 
Maleckar et al 9 , reported ongoing human studies where 28 study subjects have received 
TIL, derived from a variety of tumors, in doses ranging from 0.1 x 10 11 to 2.9 x 10 11 
without systemic rIL-2. Preliminary data appear to indicate that the TIL recognized the 
autologous tumor and specific lytic activity was observed, which appears to correlate to 
the TIL. 
Continuous infusion of rIL-2 in a dose of 1-3 x 10 6 U/m 2 per 24 hours was administered 
with TIL to 28 study subjects with advanced renal cell carcinomna, malignant melanoma 
and non-small-cell lung cancer. The results showed an objective response of 29 percent 
in the renal cell cancer and 23 percent in melanoma 4 . 
Rosenberg et al 8 , reported a Phase 1 study which showed that percent (9/15) of the study 
subjects with metastatic melanoma, treated with rIL-2 and TIL, had objective regression 
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Recombinant DNA Research, Volume 15 
