SQZ Biotechnologies Presents New eAPC Preclinical Data Demonstrating That Multiplexed mRNA Engineering of Immune Cells Increases Killer T Cell Activity In Vivo
SQZ Biotechnologies has reported significant preclinical advancements in its eAPC platform, which shows that mRNA-based expression of CD86, IL-2, and IL-12 markedly enhances CD8 T cell activity against diverse antigens, including HPV and KRAS. Data presented at the AACR 2022 Annual Meeting indicates effective T cell responses in humanized mouse models. The SQZ-eAPC-HPV candidate is currently undergoing a Phase 1/2 trial (COMMANDER-001) for HPV16+ tumors, demonstrating promising potential for improved patient outcomes through enhanced immune responses.
- Preclinical data shows substantial increase in CD8 T cell activity using eAPC technology.
- SQZ-eAPC-HPV in Phase 1/2 clinical trial for HPV16+ advanced tumors.
- Demonstrated strong T cell responses across multiple disease antigens and HLA types.
- None.
SQZ® eAPC Platform Demonstrates that mRNA-based Expression of Co-Stimulatory CD86 and Membrane-bound IL-2 and IL-12 Dramatically Increases Antigen-Specific CD8 T Cell Activity
T Cell Responses Shown Across Multiple Antigens In Vitro and In Vivo Using mRNAs that Encode Infectious Disease or Tumor-Related Antigens, including HPV (E6 and E7) and KRAS
Beyond eAPC Preclinical Advances, a SQZ AAC Phase 1/2 Clinical Trial in Progress Presentation to be Delivered on
Data Presented at the
The company’s first eAPC therapeutic candidate, SQZ-eAPC-HPV, is in a Phase 1/2 clinical trial (COMMANDER-001) in patients who have human papillomavirus positive (HPV16+) solid tumors. SQZ-eAPC-HPV delivers mRNA for HPV-specific E6 and E7 antigens, CD86 costimulatory factor, and membrane-bound IL-2 and IL-12 cytokines. This new platform represents sophisticated engineering that we believe to be an advancement over the company’s APC platform candidate, which has demonstrated promising preliminary monotherapy clinical activity in a patient with HPV16+ solid tumors.
“Our eAPC preclinical data, both in vitro and in vivo, demonstrate the synergistic potential of our multiple mRNA delivery approach on activating CD8+T cells,” said
In addition to the eAPC preclinical data, a Trial in Progress poster presentation of the ENVOY-001 Phase 1/2 clinical trial will be delivered by
AACR EAPC MRNA HIGHLIGHTS IN HUMANIZED MOUSE MODEL
Synergistic Impact of Multiple mRNA T cell Stimulators
- Mice treated with human eAPCs including mRNA for CMV antigen, CD86 costimulatory factor, and membrane-bound IL-2 and IL-12 cytokines were shown to have a dramatic increase in killer T cells compared to APCs with mRNA for antigen alone
- Mice treated with human eAPCs including mRNA for influenza (Flu) antigen, CD86 costimulatory factor, and membrane-bound IL-2 and IL-12 cytokines were shown to have a three-fold increase in killer T cell compared to APCs with mRNA for antigen alone
Strong T Cell Responses Across Multiple HLA Types
- Mice treated with human eAPCs including mRNA for CMV antigen, CD86 costimulatory factor, and membrane-bound IL-2 and IL-12 cytokines were shown to have higher killer T cells responses across a range of HLA types (A*01, A*02, A*11, A*24, B*07, B*35) compared to those squeezed with CMV peptide alone
AACR mRNA HIGHLIGHTS IN HUMAN PBMCs (B cell, T cell, NK cell, Monocytes)
Expansion of CD8 T Cells & Cytokine Signaling
- Human PBMCs with antigen-encoding mRNA for CMV, Flu, HPV16 E6, HPV16 E7 and KRAS G12V substantially increased activation of antigen-specific T cells in vitro compared to untreated PBMCs
- Membrane-bound IL-2 and IL-12 mRNA delivery in PBMC subsets led to surface expression of the cytokines and functional signaling
AACR eAPC Poster Presentation
Title: Co-delivery of antigen-encoding mRNA and signal 2/3 mRNAs to PBMCs by CellSqueeze® technology generates SQZ® eAPCs that prime CD8 T cells in humanized mouse model
Presenter:
Session Date and Time:
Poster Board Number: 19
Abstract Number: 2853
AACR Trial in Progress Presentation
Title: ENVOY-001: A phase 1, multicenter, open-label study of SQZ-AAC-HPV as monotherapy and in combination with immune checkpoint inhibitors in HLA-A*02+ patients with HPV16+ recurrent, locally advanced, or metastatic solid tumors
Presenter:
Session Date and Time:
Poster Section: 35
Abstract Number: 7645
About SQZ-AAC-HPV
SQZ® Activating Antigen Carriers (AACs), derived from engineered red blood cells (RBCs), are designed to transport tumor-specific antigens and adjuvant to a patient’s own professional antigen presenting cells (APCs). The APCs would then activate CD8 killer T cells that travel to tumor sites and attack specific diseased cells. SQZ-AAC-HPV is the company’s first AAC clinical candidate, and it is being evaluated in a Phase 1/2 clinical trial (ENVOY-001 or SQZ-AAC-HPV-101) for the treatment of HPV16+ advanced or metastatic solid tumors. The investigational candidate is being studied as a monotherapy and in combination with immune checkpoint inhibitors.
ENVOY-001 Trial Design
SQZ-AAC-HPV is being evaluated in a Phase 1/2 clinical trial (ENVOY-001) for the treatment of HPV16+ advanced or metastatic solid tumors. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with immune checkpoint inhibitors. The study consists of two parts. The first part is designed to assess the safety and tolerability of multiple doses of SQZ-AAC-HPV monotherapy in treatment-experienced patients. The second part of the study will assess safety and tolerability of SQZ-AAC-HPV in combination with nivolumab and/or ipilimumab.
About SQZ-eAPC-HPV
SQZ® Enhanced Antigen Presenting Cells (eAPC) are derived from peripheral blood mononuclear cells (PBMCs), which are primarily composed of monocytes, T cells, B cells, and NK cells, and engineered with various mRNA encoding for multiple target antigens and immuno-stimulatory signals, including CD86 and membrane-bound IL-2 and IL-12. The company has presented preclinical findings showing that SQZ eAPCs have generated robust T cell responses in human in vitro and in vivo models. Additionally, it was demonstrated that HPV16-encoding mRNA delivery to PBMCs stimulated CD8+ T cells across a range of HLA haplotypes, supporting eAPC clinical development in broader HPV16+ patient populations.
COMMANDER-001 Trial Design
SQZ-eAPC-HPV is being evaluated in a Phase 1/2 clinical trial (COMMANDER-001) for the treatment of HPV16+ advanced or metastatic solid tumors. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with pembrolizumab, an immune checkpoint inhibitor. The study consists of two parts. The first part is designed to assess safety and tolerability of multiple doses of SQZ-eAPC-HPV in treatment-experienced patients, following a dose-escalation scheme for monotherapy, and a dose de-escalation for the combination with pembrolizumab. The second part of the study will assess clinical response of SQZ-eAPC-HPV monotherapy in combination with pembrolizumab in immune checkpoint inhibitor treatment-naïve patient populations.
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
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