Q:

Adoptive immunotherapy with lymphokine activated killer cells (LAK) and tumor infiltrate (TIL) cells are characterized by:

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Adoptive immunotherapy with lymphokine activated killer cells (LAK) and tumor infiltrate (TIL) cells are characterized by:


  1. Nonspecific stimulation of effector cells.
  2. Expansion ex vivo of large numbers of lymphocytes.
  3. Infusion with interleukin 2 (IL-2).
  4. Significant toxicity at high doses.
  5. All of the above.

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E. All of the above.

 DISCUSSION: LAK cells, generated by short-term culture of peripheral blood lymphocytes in the presence of high concentrations of IL-2, lyse transformed target cells, and have minimal lytic activity for most normal tissues. Up to 10 11 in vitro generated LAK cells have been administered in a single intravenous infusion to cancer patients. Therapeutic trials have also combined short courses of high-dose systemic IL-2 administration with LAK cell transfer to promote LAK function and viability, with apparently enhanced efficacy. The shortcomings of LAK and IL-2 therapy included a larger degree of toxicity (including pulmonary, renal, and hepatobiliary) with a significant proportion of patients requiring intensive care unit admissions and 2% to 5% treatment-related mortality. Despite this, response rate remained relatively low.

Another therapy using in vitro expanded lymphocytes derived from a TIL has been evaluated in clinical trials. In humans, TIL cell lines have been generated by mincing tumor specimens and culturing eluted lymphocytes with high concentrations of IL-2. TIL lines can be expanded to 10 8 to 10 11 cells over 3 to 8 weeks in culture, and some lines appear to function as T cells with lytic specificity for autologous—but not allogeneic—tumor targets, whereas others function as LAK cells and lyse both autologous and allogeneic tumor targets. Adoptive transfer of 5 × 10 10 TIL alone has not been associated with significant toxicity, and administration of 5 × 10 10 TIL cells with concurrent systemic IL-2 has caused toxicities that are attributable to the IL-2.

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