Adoptive Cellular Therapy

Adoptive cellular immunotherapy is the transfer of cultured immune cells that have anti-tumor reactivity into a tumor-bearing host. The cells to be transferred are expanded from the lymphocytes of patients with the tumor. One protocol for adoptive cellular immunotherapy is to generate LAK cells by culturing peripheral blood leukocytes from patients with the tumor in high concentrations of IL-2, and injecting the LAK cells back into the patients (Fig. 17-8). As discussed previously, LAK cells are derived mainly from NK cells. Adoptive therapy with autologous LAK cells, in conjunction with in vivo administration of IL-2 or chemotherapeutic drugs, has yielded impressive results in mice, with regression of solid tumors. Human LAK cell therapy trials have thus far been largely restricted to advanced cases of metastatic tumors, and the efficacy of this approach appears to vary from patient to patient. A variation of this approach is to isolate TILs from the inflammatory infiltrate present in

FIGURE 17-8 Adoptive cellular therapy. In a commonly used approach for adoptive cellular therapy, lymphocytes isolated from the blood or tumor infiltrate of a patient are expanded by culture in IL-2 and are infused back into the patient. This treatment, often combined with systemic IL-2 administration, leads to tumor regression in some patients.

FIGURE 17-8 Adoptive cellular therapy. In a commonly used approach for adoptive cellular therapy, lymphocytes isolated from the blood or tumor infiltrate of a patient are expanded by culture in IL-2 and are infused back into the patient. This treatment, often combined with systemic IL-2 administration, leads to tumor regression in some patients.

and around solid tumors, obtained from surgical resection specimens, and to expand the TILs by culture in IL-2. The rationale for this approach is that TILs may be enriched for tumor-specific CTLs and for activated NK cells. TIL therapy for metastatic melanoma is now being used in many centers. Another approach for adoptive therapy now in development is T cell receptor (TCR) gene therapy in which a tumor patient's T cells are transduced in vitro with genes encoding a TCR specific for a tumor antigen, expanded, and then infused back into the patient.

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