Cancer vaccines aim to generate antigen-specific anti-tumor immune responses. However, their efficacy has been hampered by inefficient cross-presentation of the target antigens. Cell Squeeze® technology delivers target antigens directly into the PBMC’s cytosol via temporary cell membrane disruption through a microfluidic chip, which can achieve more efficient MHC-I antigen presentation compared to conventional cancer vaccines. SQZ-PBMC-HPV is an autologous cell vaccine targeting HPV16 viral oncoprotein E6 and E7 using the Cell Squeeze platform.
SQZ-PBMC-HPV-101 (NCT04084951) includes pts with advanced HPV16 cancers progressing after standard therapy who have ECOG 0-1, proper organ function, and RECIST measurable lesion(s). After leukapheresis, manufacturing of the cell product takes <24 hours with a vein-to-vein time of about 1 week. SQZ-PBMC-HPV was given IV q3w without a conditioning regimen. Double antigen priming (DP) was introduced in the last 2 cohorts. The response was assessed via RECIST 1.1. Paired biopsies were required at baseline and Day 28.
18 pts [head and neck (9), anal (7), and cervical (2)] with median 3.5 prior lines of systemic cancer therapy were dosed in 4 dose-escalation cohorts (from 0.5 to 5.0 x10e6/kg [DP]). Treatment was well-tolerated and there were no DLTs, Grade (G) >2 related SAEs or related G >3 AEs. Paired biopsies of the tumor pre- and on-therapy indicated increased CD8 T cell activity across dose levels. Out of 5 response evaluable pts in the highest dose cohort, 1 unconfirmed partial response was observed in a pt with heavily pretreated PD-1 inhibitor refractory head and neck cancer. On-treatment biopsy of this pt showed significant increase in CD8 T cell infiltrates and PD-L1 expression.
In addition to demonstrating clinical feasibility of the Cell Squeeze® technology and favorable tolerability of engineered APCs, the data suggest that SQZ-PBMC-HPV cell-based vaccine can efficiently prime CD8 T cell responses to the target antigens leading to tumor shrinkage. Detailed efficacy, safety, and correlative biomarker data will be presented.
NCT04084951.
SQZ Biotechnologies.
SQZ Biotechnologies.
J. Park: Non-Financial Interests, Personal and Institutional, Principal Investigator: SQZ Biotechnologies. J.C. Baranda: Non-Financial Interests, Personal and Institutional, Principal Investigator: SQZ Biotechnologies. M.M. Mita: Non-Financial Interests, Personal, Principal Investigator: SQZ Biotechnologies. W.T. Iams: Non-Financial Interests, Personal and Institutional, Principal Investigator: SQZ Biotechnologies. M.S. Gordon: Non-Financial Interests, Personal and Institutional, Principal Investigator: SQZ Biotechnologies. M. Taylor: Financial Interests, Personal and Institutional, Principal Investigator: SQZ Biotechnologies. N. Dhani: Non-Financial Interests, Personal and Institutional, Principal Investigator: SQZ Biotechnologies. S.M. Loughhead: Financial Interests, Personal, Full or part-time Employment: SQZ Biotechnologies. R. Ji: Financial Interests, Personal, Full or part-time Employment: SQZ Biotechnologies. R.F. Zwirtes: Financial Interests, Personal, Full or part-time Employment: SQZ Biotechnologies. M. Kornacker: Financial Interests, Personal, Full or part-time Employment: Roche. O. Rosen: Financial Interests, Personal, Officer: SQZ Biotechnologies. H. Bernstein: Financial Interests, Personal, Officer: SQZ Biotechnologies. A. Jimeno: Non-Financial Interests, Personal and Institutional, Principal Investigator: SQZ Biotechnologies.