Route of administration modulates the induction of dendritic cell vaccine-induced antigen-specific T cells in advanced melanoma patients.

It is unknown whether the route of administration influences dendritic cell (DC)-based immunotherapy. We compared the effect of intradermal versus intranodal administration of a DC vaccine on induction of immunologic responses in melanoma patients and examined whether concomitant administration of interleukin (IL)-2 increases the efficacy of the DC vaccine. HLA-A2.1(+) melanoma patients scheduled for regional lymph node dissection were vaccinated four times biweekly via intradermal or intranodal injection with 12 × 10⁶ to 17 × 10⁶ mature DCs loaded with tyrosinase and gp100 peptides together with keyhole limpet hemocyanin (KLH). Half of the patients also received low-dose IL-2 (9 MIU daily for 7 days starting 3 days after each vaccination). KLH-specific B- and T-cell responses were monitored in blood. gp100- and tyrosinase-specific T-cell responses were monitored in blood by tetramer analysis and in biopsies from delayed-type hypersensitivity (DTH) skin tests by tetramer and functional analyses with (51)Cr release assays or IFNγ release, following coculture with peptide-pulsed T2 cells or gp100- or tyrosinase-expressing tumor cells. In 19 of 43 vaccinated patients, functional tumor antigen-specific T cells could be detected. Although significantly more DCs migrated to adjacent lymph nodes upon intranodal vaccination, this was also highly variable with a complete absence of migration in 7 of 24 intranodally vaccinated patients. Intradermal vaccinations proved superior in inducing functional tumor antigen-specific T cells. Coadministration of IL-2 did not further augment the antigen-specific T-cell response but did result in higher regulatory T-cell frequencies. Intradermal vaccination resulted in superior antitumor T-cell induction when compared with intranodal vaccination. No advantage of additional IL-2 treatment could be shown.

Lesterhuis WJ ，de Vries IJ ，Schreibelt G ，Lambeck AJ ，Aarntzen EH ，Jacobs JF ，Scharenborg NM ，van de Rakt MW ，de Boer AJ ，Croockewit S ，van Rossum MM ，Mus R ，Oyen WJ ，Boerman OC ，Lucas S ，Adema GJ ，Punt CJ ，Figdor CG ... -  《-》

Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients.

de Vries IJ ，Lesterhuis WJ ，Scharenborg NM ，Engelen LP ，Ruiter DJ ，Gerritsen MJ ，Croockewit S ，Britten CM ，Torensma R ，Adema GJ ，Figdor CG ，Punt CJ ... -  《CLINICAL CANCER RESEARCH》

Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome.

de Vries IJ ，Bernsen MR ，Lesterhuis WJ ，Scharenborg NM ，Strijk SP ，Gerritsen MJ ，Ruiter DJ ，Figdor CG ，Punt CJ ，Adema GJ ... -  《JOURNAL OF CLINICAL ONCOLOGY》

Vaccination with mRNA-electroporated dendritic cells induces robust tumor antigen-specific CD4+ and CD8+ T cells responses in stage III and IV melanoma patients.

Aarntzen EH ，Schreibelt G ，Bol K ，Lesterhuis WJ ，Croockewit AJ ，de Wilt JH ，van Rossum MM ，Blokx WA ，Jacobs JF ，Duiveman-de Boer T ，Schuurhuis DH ，Mus R ，Thielemans K ，de Vries IJ ，Figdor CG ，Punt CJ ，Adema GJ ... -  《-》

Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients.

Bedrosian I ，Mick R ，Xu S ，Nisenbaum H ，Faries M ，Zhang P ，Cohen PA ，Koski G ，Czerniecki BJ ... -  《JOURNAL OF CLINICAL ONCOLOGY》