Activating Antigen Carriers (AACs) Shown Preclinically to Activate CD8 T Cells, Increase Their Tumor Infiltration and Drive Tumor Killing
Demonstrated Improved Efficacy of AAC Therapy Through Combination with Chemotherapy Agent
WATERTOWN, Mass., October 03, 2022--(BUSINESS WIRE)--SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, today announced the publication of preclinical research on the SQZ® Activating Antigen Carrier (AAC) platform. The data, published in Frontiers in Immunology, demonstrated that the company’s Cell Squeeze® platform can be used to generate AACs by engineering red blood cells (RBCs) with antigen and adjuvant that can drive antigen-specific activation of T cells both in mouse in vivo and human in vitro systems. The study also used a mouse tumor model to show that the efficacy of the AAC therapy could be further enhanced by combining with the chemotherapeutic agent, Cisplatin.
"This paper demonstrates the potential of our technology to generate an effective red blood cell-derived cancer immunotherapy," said Howard Bernstein, M.D., Ph.D., Chief Scientific Officer at SQZ Biotechnologies. "The ability of the Cell Squeeze® platform to engineer RBCs to leverage the natural process of RBC clearance for T cell activation represents a promising new therapeutic approach to cancer treatment. We look forward to building on these preclinical results in our ongoing Phase 1/2 clinical trial."
The company’s engineered RBCs are designed to transport their cargo of antigen and adjuvant to professional antigen presenting cells (APCs) in the body. The published data demonstrate that when these professional APCs process the engineered RBC, they present the desired antigen to endogenous T cells and drive their activation. This approach to generate RBC therapeutics could be tailored to deliver a variety of antigen and adjuvant materials, and other possible agents, to potentially enhance different aspects of anti-tumor immunity.
"We are excited about the preclinical findings of our AAC program, which has shown potential in both monotherapy settings and in combination with chemotherapy," said Scott Loughhead, Ph.D., VP of Translational Research at SQZ Biotechnologies. "AACs represent a truly differentiated approach that offers the opportunity for broad applicability across solid tumor types."
Generation of AACs: Investigators used the Cell Squeeze® technology to engineer RBCs with E6 and E7 antigens and the adjuvant, poly I:C. This process generates AACs that resemble aged RBCs which triggers rapid clearance by professional APCs.
Effective Delivery to APCs: The method leverages the natural process of RBC clearance to deliver tumor antigens to endogenous professional APCs without the use of chemical or viral vectors.
Antigen-Specific Activation of T cells: AAC uptake, antigen processing, and presentation by APCs drove antigen-specific activation of T cells in mouse in vivo and human in vitro systems. In a mouse model of HPV16+ tumors, AAC therapy demonstrated significant anti-tumor effects including 12-fold improvement in CD8+ T cell infiltration and 900-fold improvement in E7 antigen-specific CD8+ T cell infiltration compared to untreated animals.
Enhanced Efficacy with Addition of Cisplatin: The combination of AAC therapy and the chemotherapeutic agent Cisplatin, a common treatment for HPV-driven tumors, increased the efficacy of the treatment in a preclinical tumor model.
SQZ® AACs are generated by squeezing red blood cells (RBCs) with antigens and activating adjuvant. The process is tuned to make the engineered RBCs appear aged. Once administered to patients, SQZ® AACs aim to be rapidly taken up by professional antigen presenting cells through a natural process to destroy aged RBCs in the body known as eryptosis. After being taken up, the encapsulated antigen and adjuvant within SQZ® AACs is released, allowing for antigen processing and maturation of professional, endogenous antigen presenting cells in the lymphoid organs, and drives subsequent activation of HPV-specific T cells. SQZ-AAC-HPV is the first product candidate from the SQZ® AAC platform.
About Human Papillomavirus Positive Cancers
Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years, often leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer, HPV+ tumors account for 4.5% of all cancers worldwide resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.
About SQZ Biotechnologies
SQZ Biotechnologies is a clinical-stage biotechnology company focused on unlocking the full potential of cell therapies to benefit patients with cancer, autoimmune and infectious diseases. The company’s proprietary Cell Squeeze® technology offers the unique ability to deliver multiple biological materials into many patient cell types to engineer what we believe can be a broad range of potential therapeutics. Our goal is to create well-tolerated cell therapies that can provide therapeutic benefit for patients and improve the patient experience over existing cell therapy approaches. With accelerated production timelines under 24 hours and the opportunity to eliminate preconditioning and lengthy hospital stays, our approach could change the way people think about cell therapies. The company’s first therapeutic applications seek to generate target-specific immune responses, both in immune activation for the treatment of solid tumors and in immune tolerance for the treatment of unwanted immune reactions and autoimmune diseases. For more information, please visit www.sqzbiotech.com.
Forward Looking Statement
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements relating to events and presentations, platform and clinical development, product candidates, preclinical and clinical activities, progress and outcomes, development plans, clinical safety and efficacy results, and therapeutic potential. These forward-looking statements are based on management's current expectations. Actual results could differ from those projected in any forward-looking statements due to several risk factors. Such factors include, among others, risks and uncertainties related to our limited operating history; our significant losses incurred since inception and expectation to incur significant additional losses for the foreseeable future; the development of our initial product candidates, upon which our business is highly dependent; the impact of the COVID-19 pandemic on our operations and clinical activities; our need for additional funding and our cash runway; the lengthy, expensive, and uncertain process of clinical drug development, including uncertain outcomes of clinical trials and potential delays in regulatory approval; our ability to maintain our relationships with our third party vendors; and protection of our proprietary technology, intellectual property portfolio and the confidentiality of our trade secrets. These and other important factors discussed under the caption "Risk Factors" in our Annual Report on Form 10-K and other filings with the U.S. Securities and Exchange Commission could cause actual results to differ materially from those indicated by the forward-looking statements. Any forward-looking statements represent management's estimates as of this date and SQZ undertakes no duty to update these forward-looking statements, whether as a result of new information, the occurrence of current events, or otherwise, unless required by law.
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