Multiple Immune Cell Types – T cells, B cells, NK cells, and Monocytes – Demonstrate Engineering of MHC-I Antigen Presentation
Paper on the Company’s Cell Squeeze® Platform’s Cell Engineering Capabilities Published in the February 15th Edition of Journal of Immunology
SQZ Biotechnologies (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, today announced the publication of comprehensive preclinical research on the company’s ability to engineer multiple immune cell types to drive MHC-I antigen presentation, a critical advance in the ability to drive a patient’s killer T cells to fight multiple diseases. The cell engineering findings, published online and in the February 15th edition of the Journal of Immunology, are part of the body of work supporting the development of SQZ® Antigen Presenting Cell (APC) and SQZ® Enhanced Antigen Presenting Cell (eAPC) cancer vaccine therapeutic programs currently in clinical development.
The journal publication follows the December 2021 oral presentation at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) congress reporting that the company’s lead APC therapeutic candidate induced a radiographic, symptomatic, histologic response as a monotherapy in a late line head and neck cancer patient.
“We are excited to publish the comprehensive dataset that has long underpinned our conviction in the SQZ APC platform’s potential for patient impact,” said Armon Sharei, Ph.D., Chief Executive Officer and Founder of SQZ Biotechnologies. “These data demonstrate the ability of microfluidic squeezing to engineer antigen presentation in T cells, B cells, NK cells, and monocytes, thereby empowering these immune cells to activate endogenous CD8 killer T cells - a powerful and highly specific arm of the immune system. Our early clinical trial data presented at ESMO-IO demonstrated our multi-cell engineering mechanism at work, and we are excited about the potential to implement this approach across multiple tumor types.”
CD8, or Killer, T cells play a critical role in combating diseases, however, a major bottleneck for CD8 T cell activation is displaying the desired disease associated antigen(s) to these T cells through the MHC-I pathway. In this journal article, SQZ scientists and their collaborators describe how they overcome this fundamental biological problem through the delivery of antigens directly into the cytosol of immune cells by microfluidic squeezing.
“What’s exciting about our platform is the ability to efficiently insert many types of antigen cargo directly into a cell’s cytosol for presentation to killer T cells, and the ability to engineer other immune system cells to target disease,” said Howard Bernstein, M.D., Ph.D., chief scientific officer at SQZ Biotechnologies. “Our enhanced APCs, which recently received FDA IND clearance to commence a clinical trial, represent a further advancement of the concept by delivering five different mRNAs into a patient’s monocytes, B cells, T cells, and NK cells in a single step. We are exploring an exciting frontier in cell therapy and look forward to assessing its potential for patient impact in our clinical trials.”
Major Journal Study Findings
Enabling Cancer Vaccine Development
- In this study, the authors demonstrate preclinically that cytosolic delivery of antigens through microfluidic squeezing enables direct MHC-I antigen presentation to CD8 T cells by diverse immune system cell types, overcoming a major challenge in the development of cancer vaccine therapeutics
- Study authors also showed they could expand beyond the more commonly used dendritic cells to induce T cell activation. MHC-I presentation was demonstrated in engineered T cells, B cells, Natural Killer cells, and monocytes – broadening their potential use and impact in therapeutic design
Tumor Protection and Immunization
- In vivo study findings showed that engineered B cells, T cells, or mixed peripheral blood mononuclear cells (PBMCs), were all capable of activating endogenous immune responses across multiple antigens
- These immune responses were able to protect mice in prophylactic studies, drive tumor regression in therapeutic studies, and form long-term memory that protects against future tumor challenge
- Authors further found that this protection correlates with tumor infiltration of antigen-specific cells with nearly 90 percent of infiltrating CD8 T cells being specific for the tumor antigen delivered using the Cell Squeeze® technology
Efficient, Scaled Manufacturing
- Study authors compared the viability and delivery of engineered cells using research-scale and manufacturing-scale Cell Squeeze® chips. They found that delivery of different cells types within PBMCs was similar across research-scale and manufacturing-scale chips, and study authors demonstrated successful increase from millions to billions of cells processed using manufacturing-scale chips
About SQZ Biotechnologies
SQZ Biotechnologies Company is a clinical-stage biotechnology company focused on unlocking the full potential of cell therapies for patients around the world and has active programs in Oncology, Autoimmune and Infectious Diseases, as well as additional exploratory initiatives to support future pipeline growth. The company’s proprietary Cell Squeeze® technology offers the unique ability to deliver multiple biological materials into many cell types to engineer what we believe can be a broad range of potential therapeutics. With demonstrated production timelines under 24 hours and the opportunity to eliminate preconditioning and lengthy hospital stays, our approach could significantly broaden the therapeutic range and accessibility of cell therapies. The company’s first therapeutic applications seek to generate target-specific immune responses, both in activation for the treatment of solid tumors and infectious diseases, and in immune tolerance for the treatment of autoimmune diseases. For more information, please visit www.sqzbiotech.com.
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