Evaluation of the Sentinel Immunized Node for Immune Monitoring of Cancer Vaccines

Abstract

Background-We hypothesized that lymph nodes draining sites of cutaneous vaccination could be identified by sentinel node biopsy techniques, and that measuring T-cell response with lymphocytes obtained from these lymph nodes would provide a more sensitive measure of immunogenicity than would the same measurement made with peripheral blood lymphocytes (PBL).

Paradoxical Decrease in the Capture and Lymph Node Delivery of Cancer Vaccine Antigen Induced by a TLR4 Agonist as Visualized by Dual-Mode Imaging

“…Free SPIO particles are observed in the DLN immediately after injection resulting in a total blackout of the DLN, while APC-internalized SPIO particles appear in the DLN within 3 days followed by a progressive increase. As we previously reported in the mouse(14), the ability to use magnetic selection of APCs that have captured antigen also provides an unprecedented opportunity to probe the relevant APC populations in clinical therapeutic cancer vaccine trials where DLN sampling is part of the biomarker assessment strategy (32)…”

Immune-Therapy in Cutaneous Melanoma – Efficacy Immune Markers

“…The processes that induce effective antitumour immunity by cancer vaccines implie several events: antigen delivery to antigen-presenting cells, migration of dendritic cells that carry the processed antigen to draining lymph nodes, antigen presentation to circulating T cells that enter the lymph nodes through the high endothelial venules, expansion of antigen reactive T-cells in the lymph nodes, dissemination of specific T-cells to tumour site, and tumour destruction by activated tumour-reactive T-cells (Slingluff Jr et al, 2008).…”

“…In that case, the vaccination "failure" conclusion is not true as it did not have the chance to even naturally develop. To overcome this, it has been proposed that measuring the T-cell response from lymph nodes draining the cutaneous sites of vaccination could be a sensitive assessment of immunogenicity developed by a melanoma vaccine administration (Slingluff Jr et al, 2008). regressions in 41% of patients, but T-cell responses were registered in only a small minority of patients (Rosenberg et al, 1998).…”

“…Nevertheless, optimization of cancer vaccines will benefit from complex immune monitoring in multiple lymphoid compartments. Critical compartments for immune monitoring are comprising the lymph node as the site of T-cell response induction, the circulating peripheral blood lymphocytes (PBL) and the sites of primary and metastatic tumour as well (Slingluff Jr et al, 2008). Cancer vaccine clinical trials meant to induce T cell -mediated immunity are evaluated routinely by measuring the immune response in the PBL but not in the other two compartments.…”

“…Some murine and human studies suggest that, even after a single immunization, epidermal Langerhans cells migrate and mature to draining nodes within hours, with a peak of T-cell accumulation in the draining lymph nodes at day 5-10 ( Macatonia et al, 1987;Rosato et al, 1996;Yoshizawa et al, 1991). Thus, it has been hypothesized that evaluation of T-cell responses in the draining lymph node would permit a more sensitive measure of immunogenicity than evaluation of T-cell responses in the peripheral blood alone (Slingluff Jr et al, 2008). From patients enrolled in clinical trials of experimental melanoma peptide vaccines, sentinel immunized nodes (SIN) were harvested a week after the third vaccine round, in order to identify the peak time of T-cell accumulation.…”