A5014800092- Cancer Immunotherapy and Biomarkers
- Esophageal Cancer Research and Treatment
- Immune cells in cancer
- Chronic Disease Management Strategies
- Primary Care and Health Outcomes
- Cancer Cells and Metastasis
- Monoclonal and Polyclonal Antibodies Research
- Ferroptosis and cancer prognosis
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Pancreatic and Hepatic Oncology Research
- Diabetes Management and Education
- Nutritional Studies and Diet
- Health Systems, Economic Evaluations, Quality of Life
- Immune Cell Function and Interaction
- Food Security and Health in Diverse Populations
- Colorectal Cancer Screening and Detection
University of California, San Francisco
2024
UCSF Helen Diller Family Comprehensive Cancer Center
2024
University of Mississippi Medical Center
2022
Tulane University
2020
Abstract Sotigalimab is an agonistic anti-CD40 mAb that can modulate antitumor immune responses. In a phase II clinical trial of sotigalimab combined with neoadjuvant chemoradiation (CRT) in locally advanced esophageal/gastroesophageal junction (E/GEJ) cancer the primary outcome efficacy as measured by pathologic complete response (pCR) rate, combination induced pCR 38% treated patients. We investigated mechanism action samples obtained from this trial. Tumor biopsies and peripheral blood...
<p>Tumor-infiltrating myeloid cells are activated post-sotigalimab with alterations in antigen processing and metabolic pathways. <b>A,</b> MIBI analysis depicts changes cell density upregulation of activation markers for DCs the TME (representative image: patient 04). <b>B,</b> Quantification DC tumor pre- by total specific subset (pre <i>n</i> = 5, post 4). <b>C,</b> CD86, HLA-II, CD40 expression all post-treatment <b>D</b>...
<p>Treatment with sotigalimab increases immune infiltration into the TME, including T cells and myeloid cells. <b>A,</b> Patients were treated at initiation of study (a), beginning week 3 (b) 8 (c). Chemotherapy radiation initiated after second dose (b). Tissue biopsies blood samples collected timepoints pre-treatment, 3, surgery. Blood used to assess changes peripheral system using CyTOF (<a href="#bib1" target="_blank">1</a>) scRNAseq href="#bib3"...
<p>Sotigalimab results in immunomodulation and apoptosis of tumor cells. <b>A,</b> Tumor cells the TME were characterized using MIBI analysis keratin, HLA-I, HLA-II, PD-L1, CD40 (representative image: patient 04). <b>B,</b> Quantification cell density by (pre <i>n</i> = 5, post 4). <b>C–E,</b> Expression phenotypic markers was also quantified for HLA I II (C), PD-L1 (D), (E; pre <b>F–H,</b> Differential expression timepoint...
<p>Sotigalimab induces an activated T cell infiltrate and reduces Tregs in tumors. <b>A,</b> Characterization of subsets the TME was done by MIBI analysis using markers for DNA, keratin, CD4, CD8, CD45RO, Foxp3, Granzyme B (GZMB; representative image: patient 04). <b>B,</b> Percentage each are shown samples pre- post-treatment, out total intratumoral cells, as analyzed (pre <i>n</i> = 5, post 4). <b>C,</b> Ki67 expression all...
<p>Supplementary Figure 4</p>
<p>Supplementary Figure 2</p>
<p>Sotigalimab induces an activated T cell infiltrate and reduces Tregs in tumors. <b>A,</b> Characterization of subsets the TME was done by MIBI analysis using markers for DNA, keratin, CD4, CD8, CD45RO, Foxp3, Granzyme B (GZMB; representative image: patient 04). <b>B,</b> Percentage each are shown samples pre- post-treatment, out total intratumoral cells, as analyzed (pre <i>n</i> = 5, post 4). <b>C,</b> Ki67 expression all...
<p>Supplementary Figure 4</p>
<p>Sotigalimab induces activation and trafficking of immune cells within the blood. <b>A</b> <b>B,</b> Heat maps cell frequency surface marker expression as analyzed by CyTOF for T NK (A) antigen-presenting (B; pre <i>n</i> = 6, post 6). The count column shows number in each cluster. “frequency signif” columns indicates statistical significance differences which there were none. Red blue protein indicate significant up- or down-regulation indicated...
<p>Treatment with sotigalimab increases immune infiltration into the TME, including T cells and myeloid cells. <b>A,</b> Patients were treated at initiation of study (a), beginning week 3 (b) 8 (c). Chemotherapy radiation initiated after second dose (b). Tissue biopsies blood samples collected timepoints pre-treatment, 3, surgery. Blood used to assess changes peripheral system using CyTOF (<a href="#bib1" target="_blank">1</a>) scRNAseq href="#bib3"...
<p>Tumor-infiltrating myeloid cells are activated post-sotigalimab with alterations in antigen processing and metabolic pathways. <b>A,</b> MIBI analysis depicts changes cell density upregulation of activation markers for DCs the TME (representative image: patient 04). <b>B,</b> Quantification DC tumor pre- by total specific subset (pre <i>n</i> = 5, post 4). <b>C,</b> CD86, HLA-II, CD40 expression all post-treatment <b>D</b>...
<p>Sotigalimab induces activation and trafficking of immune cells within the blood. <b>A</b> <b>B,</b> Heat maps cell frequency surface marker expression as analyzed by CyTOF for T NK (A) antigen-presenting (B; pre <i>n</i> = 6, post 6). The count column shows number in each cluster. “frequency signif” columns indicates statistical significance differences which there were none. Red blue protein indicate significant up- or down-regulation indicated...
<p>Supplementary Figure 1</p>
<p>Supplementary Figure 2</p>
<p>Sotigalimab results in immunomodulation and apoptosis of tumor cells. <b>A,</b> Tumor cells the TME were characterized using MIBI analysis keratin, HLA-I, HLA-II, PD-L1, CD40 (representative image: patient 04). <b>B,</b> Quantification cell density by (pre <i>n</i> = 5, post 4). <b>C–E,</b> Expression phenotypic markers was also quantified for HLA I II (C), PD-L1 (D), (E; pre <b>F–H,</b> Differential expression timepoint...
<p>Supplementary Figure 5</p>
<p>Supplementary Figure 1</p>
<div>Abstract<p>Sotigalimab is an agonistic anti-CD40 mAb that can modulate antitumor immune responses. In a phase II clinical trial of sotigalimab combined with neoadjuvant chemoradiation (CRT) in locally advanced esophageal/gastroesophageal junction (E/GEJ) cancer the primary outcome efficacy as measured by pathologic complete response (pCR) rate, combination induced pCR 38% treated patients. We investigated mechanism action samples obtained from this trial. Tumor biopsies and...