This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.
Adoptive transfer of ex vivo expanded tumor-specific T cells is a promising therapeutic modality for promoting or augmenting antitumor immunity. Several groups, including ours, are developing antigen receptor gene transfer strategies as a means of generating effector cells for adoptive therapy. Chimeric antigen receptors (CARs) have been described that use single-chain antibodies or cytokine ligands as tumor targeting domains. Here, we describe the capacity of a tumor-binding peptide identified by phage display combinatorial library screening to serve as a CAR targeting domain. A phage library-selected high-affinity 12-mer peptide (Bpep) specific for alpha(v) beta(6) integrin (avb6) was chosen for these studies. Primary human T cells were genetically modified to express the Bpep-CAR consisting of an avb6-specific peptide and human IgG4 hinge-Fc extracellular domain fused to the cytoplasmic tail of CD3-z. T cell expression of the Bpep-CAR was assessed by Western blot analysis, and trafficking of the Bpep-CAR to the cell surface was demonstrated by flow cytometry. Functionally, Bpep-CAR redirected cytotoxic T lymphocytes specifically kill integrin avb6 þ ovarian tumor targets, and are activated for interferon gamma secretion. Our data suggest that large new repertoires of tumor-specific T cell antigen receptor transgenes might be available through merging combinatorial peptide libraries with CAR construct design.
Introduction. Sentinel lymph node (SLN) biopsy is a vital component of staging and management of multiple cancers. The current gold standard utilizes technetium 99 (tech99) and a blue dye to detect regional nodes. While the success rate is typically over 90%, these two methods can be inconclusive or inconvenient for both patient and surgeon. We evaluated a new technique using laser-assisted ICG dye lymphangiography to identify SLN. Methods. In this retrospective analysis, we identified patients with melanoma who were candidates for SLN biopsy. In addition to tech99 and methylene blue, patients received a dermal injection of indocyanine green (ICG). The infrared signal was detected with the SPY machine (Novadaq), and nodes positive by any method were excised. Results. A total of 15 patients were evaluated, with 40 SLNs removed. Four patients were found to have nodal metastases on final pathology. 100% of these 4 nodes were identified by ICG, while only 75% (3/4) were positive for tech99 and/or methylene blue. Furthermore, none of the nodes missed by ICG (4/40) had malignant cells. Conclusion. ICG dye lymphangiography is a reasonable alternative for locating SLNs in patients with melanoma. Prospective studies are needed to better ascertain the full functionality of this technique.
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