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To: tnsaf who wrote (1463)2/3/2002 5:21:55 PM
From: tnsaf  Read Replies (1) | Respond to of 7143
 
Tumor lysate-pulsed dendritic cells can elicit an effective antitumor immune response during early lymphoid recovery

W. Asavaroengchai*,, Y. Kotera, and J. J. Mulé,§,¶
Departments of * Pathology, Surgery, and § Internal Medicine, University of Michigan Medical Center, 1520 MSRB-I, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0666

Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 2, 931-936, January 22, 2002

Dendritic cells (DC) can serve to immunize the newborn immune system to foreign antigen. In a lymphopenic environment, naive T cells undergoing homeostasis-driven proliferation can acquire increased sensitivity to antigen stimulation. Here, we evaluated the capacity of DC to effectively prime the host immune system to elicit antitumor effects in the setting of early lymphoid reconstitution after bone marrow transplantation (BMT). Indeed, bone marrow-derived, cytokine-driven DC pulsed with whole tumor lysates (TP-DC) could, early on, prime a specific and long-lasting antitumor immune response, which mediated the rejection of a lethal challenge of a weakly immunogenic breast tumor. In the therapeutic setting, TP-DC could also inhibit the growth of preexisting breast tumor metastases by repetitive immunizations initiated early after BMT. Spleen T cells obtained from mice immunized with TP-DC early after BMT showed a substantial increase in tumor-specific IFN- production. Our findings demonstrate that it is possible to promote effective antitumor immunity in a defined lymphopenic environment through DC-based immunization.

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Present address: Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114-2698.

www.pnas.org/cgi/doi/10.1073/pnas.022634999