<p>Supplementary Figure 1 (A) OGAP® Screen of tumor and non-tumorous (normal, non-diseased tissues). (B) B7-H6 mRNA expression in gastrointestinal cancer tissues (TCGA). Supplementary Figure 2 B7-H6 expression on cell lines Supplementary Figure 3 Influence of B7-H6/CD3 ITE on the B7-H6-induced activation of NK-92® MI cells. Supplementary Figure 4 Pharmacokinetic profile in NOG mice.</p>
<div>AbstractPurpose:<p>Advanced-stage gastrointestinal cancers represent a high unmet need requiring new effective therapies. We investigated the antitumor activity of a novel T cell–engaging antibody (B7-H6/CD3 ITE) targeting B7-H6, a tumor-associated antigen that is expressed in gastrointestinal tumors.</p>Experimental Design:<p>Membrane proteomics and IHC analysis identified B7-H6 as a tumor-associated antigen in gastrointestinal tumor tissues with no to very little expression in normal tissues. The antitumor activity and mode of action of B7-H6/CD3 ITE was evaluated in <i>in vitro</i> coculture assays, in humanized mouse tumor models, and in colorectal cancer precision cut tumor slice cultures.</p>Results:<p>B7-H6 expression was detected in 98% of colorectal cancer, 77% of gastric cancer, and 63% of pancreatic cancer tissue samples. B7-H6/CD3 ITE-mediated redirection of T cells toward B7-H6–positive tumor cells resulted in B7-H6–dependent lysis of tumor cells, activation and proliferation of T cells, and cytokine secretion in <i>in vitro</i> coculture assays, and infiltration of T cells into tumor tissues associated with tumor regression in <i>in vivo</i> colorectal cancer models. In primary patient-derived colorectal cancer precision-cut tumor slice cultures, treatment with B7-H6/CD3 ITE elicited cytokine secretion by endogenous tumor-infiltrating immune cells. Combination with anti-PD-1 further enhanced the activity of the B7-H6/CD3 ITE.</p>Conclusion:<p>These data highlight the potential of the B7-H6/CD3 ITE to induce T cell–redirected lysis of tumor cells and recruitment of T cells into noninflamed tumor tissues, leading to antitumor activity in <i>in vitro, in vivo</i>, and human tumor slice cultures, which supports further evaluation in a clinical study.</p></div>
Based on the modal analysis method, we developed a model that describes the output beam of a diode‐pumped solid state (DPSS) laser emitting a multimode beam. Measuring the output beam profile in the near field and at the constructed far field the individual modes, their respective contributions, and their optical parameters are determined. Using this information, the beam is optically reshaped into a quasi‐Gaussian beam by the interference and superposition of the various modes. This process is controlled by a mode modulator unit that includes different meso‐aspheric elements and a soft‐aperture. The converted beam is guided into a second optical unit comprising achromatic‐aspheric elements to produce a thin light sheet for ultramicroscopy. We found that this light sheet is markedly thinner and exhibits less side shoulders compared with a light sheet directly generated from the output of a DPSS multimode laser.
The overexpression of the translocator protein (TSPO) has been amply reported for a variety of conditions, including neurodegenerative disorders, heart failure, and cancer. Thus, TSPO has been proposed as an excellent imaging biomarker, allowing, in this manner, to obtain an accurate diagnosis and to follow disease progression and therapy response. Accordingly, several radioligands have been developed to accomplish this purpose. In this work, we selected [18F]FEPPA, as one of the clinical established tracers, and assessed its in vitro performance in colorectal cancer. Moreover, we setup an improved radiosynthesis method and assessed the in vitro binding affinity of the nonradioactive ligand toward the human TSPO. Our results show an excellent to moderate affinity, in the subnanomolar and nanomolar range, as well as the suitability of [18F]FEPPA as an imaging agent for the TSPO in colorectal cancer.
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