Background: PD-1/PD-L1 inhibitors do not show activity in mismatch repair proficient (MMRp) colorectal cancer. Inhibition of C-C motif chemokine receptor 5 (CCR5) leads to an antitumoral activation of macrophages, affecting immune cell infiltrates. PICCASSO is a phase I trial exploring safety and efficacy of pembrolizumab and maraviroc in refractory MMRp CRC.
View Article and Find Full Text PDFBackground: In patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC), immune checkpoint blockade is ineffective, and combinatorial approaches enhancing immunogenicity need exploration.
Methods: We treated 43 patients with predominantly microsatellite stable wild-type mCRC on a phase II trial combining chemotherapy with the epidermal growth factor receptor antibody cetuximab and the programmed cell death ligand 1 (PD-L1) antibody avelumab. We performed next-generation gene panel sequencing for mutational typing of tumors and liquid biopsy monitoring as well as digital droplet PCR to confirm individual mutations.
The integral synaptic vesicle protein SV31 has been shown to bind divalent cations. Here, we demonstrate that SV31 protein synthesized within a cell-free system binds Zn and to a lower extent Ni and Cu ions. Expression with Zn stabilized the protein and increased solubility.
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