A new technology for producing activated antigen carrier cells (AACs) for cancer immunotherapy was presented by the biotechnology company SQZ Biotech at the Society for Immunotherapy of Cancer (SITC) meeting in Maryland in November 2019.1
The innovative technique uses a microfluidics platform to introduce antigen and adjuvant to red blood cells (RBCs), which are then introduced to the patient and engulfed by antigen-presenting cells in order to generate a T-cell response. The company presented preclinical data at SITC, detailing the steps of the new production technique and showing data from preliminary mouse model work.
SQZ chose to first test the therapy on the TC-1 tumor model of human papillomavirus (HPV)-positive cancers, a common target, as the E6 and E7 HPV tumor antigens are unique to tumors and absent on healthy cells. The preliminary data show that in mice, the engineered AACs are briskly taken up and engulfed by macrophages and dendritic cells, resulting in clearance from the blood within 60 minutes.
“When you inject the engineered cells in mice, they get taken up very quickly within the phagocytic cells within the hour. We see powerful CD8 T-cell responses and CD4 T-cell responses. These CD8 responses subsequently infiltrate the tumor and drive a very strong tumor regression,” said Armon Sharei, PhD, SQZ CEO and cofounder.
The team implanted a tumor cell line in mice before treating them with engineered AACs after 10 days. Analysis of the tumor-infiltrating lymphocytes in these mice showed that approximately 70% of them were specific for the antigen introduced by the engineered AACs.
“If I read the data correctly, what they report is that in that experiment, the vast majority of the T cells in the tumor were specific for the peptide in the tumor cells. This is remarkable, as this is evidence for a very specific effect,” said Christian Ottensmeier, MD, PhD, professor of experimental medicine at the University of Southampton in the U.K.
The AAC treatment also increased survival and reduced tumor volume in some of the tumor-engrafted mice — but the results were perhaps a little underwhelming considering the high specificity of the reported T-cell response.
“Only about 50% of the mice survived; that is less than I would have expected for such an impressive T-cell response,” said Dr Ottensmeier. “The experiments need to be expanded upon to further investigate this discrepancy. Why are the T cells only tackling the tumor effectively in 50% of the mice?”
The work is only preliminary, but several questions will be addressed in a planned clinical trial, adding to a similar, ongoing trial using peripheral blood mononuclear cells targeting HPV-positive solid tumors (ClinicalTrials.gov Identifier: NCT04084951). On January 30, 2020, SQZ announced that the first patient in its phase 1 trial of SQZ-PBMC-HPV had been dosed. It is the first trial advancing into the clinic that was part of the 2018 SQZ-Roche collaboration, which will focus on antigen-presenting cells in oncology.2