Can We Define the Mechanism of Antitumor Response Observed During Clinical Adoptive Immunotherapy?

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Recent reports ( 1 , 2 ) have raised interest in the use of immunization with tumor cell vaccines to treat melanoma and renal cell carcinoma (RCC). Such vaccines can be used to generate specific T cells from draining lymph nodes ( 1 , 3 ). Chang et al. ( 1 ) have shown the feasibility of activating and expanding these cells ex vivo to large numbers over a short interval and some efficacy of these cells after reinjection into the patients.

Nevertheless, the mechanism of antitumor response during adoptive immunotherapy is unclear. We ( 4 ) previously reported the results of a gene-marking study of tumor-infiltrating lymphocytes (TILs) in patients with melanoma or RCC. In that study, we demonstrated long-term survival of cells after reinjection but no selective homing at tumor sites. Economou et al. ( 5 ) confirmed those results.

More recently, delayed-type hyper-sensitivity (DTH) to autologous tumor cells served as a qualitative measurement of T-cell response in a dose-escalation trial with granulocyte—macrophage colony-stimulating factor (GM-CSF)-transduced autologous RCC cells ( 6 ). Important DTH reactivity was noted at the highest dose levels, and a partial response (at least 50% reduction in all measurable lesions) was observed in a patient who displayed the largest DTH conversion; in biopsy specimens, cellular infiltration with mononuclear cells and perivascular cuffing by lymphocytes were observed. Although the T-cell repertoire has not been precisely analyzed, this reaction has been interpreted as a qualitative assessment of the T-cell response to GM-CSF genetransduced vaccine.