SQZ® Enhanced APC (SQZ® eAPC) Platform
Training Killer T Cells to Attack Solid Tumors
Putting A Patient’s Immune System to Work
A patient’s own immune system can act as a powerful weapon against their cancer. Killer T cells, for example, can be activated to identify specific targets on solid tumors and attack the cancer. By harnessing the power of Antigen Presenting Cells (APCs), which are physiologically responsible for stimulating killer T cells, our therapeutic platform could potentially halt the progression of disease.
The focus of the SQZ® enhanced Antigen Presenting Cell (eAPC) program is to provide instructions to a patient’s immune system to help it activate killer T cells against solid tumor targets and, through combination approach or cell engineering, to provide additional enhanced immunological functions to support this attack.
A Differentiated Approach
Our candidate shares instructions to CD8 Killer T Cells to target disease via the MHC-I handshake
ENGAGING THE PRIMARY T CELL ACTIVATION SIGNAL
Engaging the primary T cell activation signal requires the T cells to interact with signals produced by APCs. Through direct delivery to the cytosol, our eAPC candidate can interact with the MHC-I antigen presentation pathway, a primary signaling avenue for sharing new instructions to killer T cells.
SQZ® eAPCs – Engaging All Three T Cell Activation Signals
SQZ® eAPCs leverage a potentially more powerful handshake that engages all three signals
Our enhanced Antigen Presenting Cells (eAPCs) leverage our first-generation approach by engineering cells with tumor-specific antigens, costimulatory molecules and membrane-bound cytokines. In doing so, our eAPC product candidate engages all three signals (MHC-I antigen presentation, costimulation, cytokine pathways) used by APCs to potently activate T cells. In preclinical models, SQZ® eAPCs have been shown to generate robust killer T cell responses.
Engineering SQZ® eAPCs to Stimulate Killer T Cells Against Solid Tumors
Patient immune cells—white blood cells primarily consisting of T cells, B cells, natural killer (NK) cells, and monocytes—are collected.
The cells are squeezed with mRNA encoding for tumor-specific antigens, costimulatory molecules, and membrane-bound cytokines to create SQZ® eAPCs. The mRNA is delivered directly into the cytosol of cells, potentially allowing for more effective presentation.
When delivered into the patient, SQZ® eAPCs home to lymphoid organs and present antigen via the MHC-I mediated antigen presentation pathway—the preferred way to share new instructions to killer T cells. The costimulatory molecules and membrane-bound cytokines have the potential to improve the quantity and quality of T cell response.
The activated T cells proliferate and are designed to travel to and infiltrate solid tumors.
Clinical Development Program
Our SQZ® eAPC clinical candidate is in an active Phase 1/2 clinical trial for the treatment of patients with HPV16 positive advanced or metastatic solid tumors. HPV infection plays a significant role in the formation of anal and cervical cancers and most cases of vaginal, oropharyngeal, vulval and penile cancers – resulting in approximately 630,000 new diagnosed cases worldwide every year.
SQZ® eAPC Phase 1/2 Trial
Our SQZ® enhanced APC (eAPC) Phase 1/2 trial
(COMMANDER-001) for HPV16+ solid tumors is enrolling in its dose escalation monotherapy phase. Learn more about how this therapeutic candidate uses a patient’s own white blood cells and multiple mRNAs to activate CD8 T cells against disease.
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Future Potential Portfolio Expansion
The SQZ® eAPC platform has preclinically demonstrated the potential to induce robust immune responses against a broad range of tumor targets. The platform has the potential to expand into additional areas such as mutant KRAS, mutant TP53, EBV, HBV, and other patient-specific antigens.
SQZ® Published Research
· Initial safety data from a phase I/II dose escalation/expansion study of SQZ-eAPC-HPV, a cell-based mRNA therapeutic cancer vaccine for HPV16+ solid tumors
· SQZ® eAPCs engineered with multiple mRNA encoding for disease-specific antigens and immune stimulators had a synergistic effect that substantially increased killer T cells in humanized mouse model.
Journal of Immunology, 2022
· SQZ® APC, our first generation approach, and SQZ® eAPC preclinical data demonstrates ability to overcome fundamental biological barrier to effective and efficient killer T cell activation
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