Intratumoral injection of dendritic cells derived in vitro in patients with metastatic cancer

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Abstract
BACKGROUND Dendritic cells (DCs) are potent initiators of immune responses, and the infiltration of DCs into tumors may confer an improved prognosis. Whether the injection of DCs directly into tumors can mediate biologic activity was examined. METHODS Patients with metastatic dermal or subcutaneous tumors received granulocyte‐macrophage–colony stimulating factor to increase the numbers of peripheral blood monocyte precursors. DCs were then generated from monocytes obtained by phlebotomy with granulocyte‐macrophage–colony stimulating factor and interleukin‐4 in autologous plasma. Tumors were injected at multiple sites with 30 million autologous DCs per tumor. RESULTS Seven patients with melanoma and three patients with breast carcinoma were treated. Injections were well tolerated. Regression of the injected tumors, beginning as early as 4 days after injection, was observed in four patients with melanoma and in two patients with breast carcinoma. Biopsies of regressing lesions showed lymphocyte infiltration associated with DCs and necrosis. Neutrophils and macrophages were not evident. Lymphocytes expanded from the regressing tumors proliferated in response to heat shock proteins, HSP70 and gp96, derived from autologous tumor. The DCs injected produced interferon‐α and expressed Fas ligand mRNA but did not exhibit cytolytic activity in vitro. Expression of the costimulatory molecule, B7‐2 (CD86), decreased on DCs after intratumoral injection. CONCLUSIONS This pilot study demonstrates that DCs derived in vitro can exist viably after intratumoral injection and can mediate biologic activity in situ. Tumor‐derived heat shock proteins may be involved in the antitumor activity observed. Cancer 2000;89:2646–54. © 2000 American Cancer Society.