(The FASEB Journal. 2008;22:lb514)
© 2008 FASEB
Depletion of CD25+ T cells inhibits CD8+ T cells clonal expansion and glioblastoma multiforme regression.
James F Curtin,
Tamer M Fakhouri,
Marianela Candolfi,
Anderson Alden,
Matthew R Edwards,
Chunyan Liu,
Pedro R Lowenstein and
Maria G Castro
Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
ABSTRACT
Transient elimination of Tregs using CD25 depleting antibodies (e.g. PC61) has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are proposed to determine whether transient Treg depletion can elicit more potent anti-tumor immune responses. In this study we used a syngeneic mouse GBM model to investigate if depletion of Tregs using PC61 would also deplete activated, tumor antigen specific T cells and inhibit the generation of immune responses against brain tumor antigen. Depletion of Tregs induced brain tumor regression in untreated mice. Administration of PC61 24 d after tumor implantation (7 days after intratumoral delivery of Adenoviral vectors expressing Flt3L and TK) completely inhibited T cell dependent tumor regression. Instead of synergizing with our immunotherapy, PC61 depleted activated (CD25+) T cells and completely inhibited the clonal expansion of tumor antigen specific T cells in response to Flt3L and TK. Our results suggest that PC61 depletion is not a suitable approach when used in combination with glioma immunotherapeutic strategies.
Supported by NIH/NINDS: 1R01 NS44556.01, NS445561.01; 1R21-NSO54143.01; 1UO1 NS052465.01, 1 RO3 TW006273-01 to MGC. NIH/NINDS: 1 RO1 NS 054193.01; RO1 NS 42893.01, U54 NS045309-01 and 1R21 NS047298-01 to PRL. NIH/NINDS 1F32 NS058156.01 to MC.
