On November 12, 2021 SQZ Biotechnologies (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, reported that new SQZ AAC and eAPC preclinical research describing the robust potential of these platforms to treat cancer, including data demonstrating synergistic activity when combined with chemotherapy (Press release, SQZ Biotech, NOV 12, 2021, View Source [SID1234595461]). The company also presented new research on the development of enhanced tumor infiltrating lymphocytes (TILs) that show increased potency in the absence of exogenous cytokine (IL-2) support. The data was presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) being held November 10-14, 2021, in Washington, D.C. and virtually.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"Our presentations at SITC (Free SITC Whitepaper) provide compelling new preclinical data on the multiple biologically diverse, directed immunity approaches that we are pursuing for cancer therapies," said Howard Bernstein, M.D., Ph.D., Chief Scientific Officer at SQZ Biotechnologies. "Our AAC and eAPC platform work provides translational insights that are relevant to clinical development, including combination chemotherapy and potential expansion to broader patient populations and tumor types."
"We are also excited to present initial preclinical results on enhanced tumor infiltrating lymphocytes, highlighting a potential future therapeutic avenue," said Jonathan Gilbert, Ph.D., Vice President and Head of Exploratory Research, SQZ Biotechnologies. "Working with tumor reactive TILs provided by AgonOx, Inc., we developed mRNA engineered TILs that can proliferate and kill matched patient tumor cells in the absence of exogenous IL-2 cytokine support. Engineered TILs may enable the removal of toxic preconditioning and systemic IL-2 use with TIL therapies, making them more broadly applicable to patients."
Major Findings from Preclinical Research
Poster #156: RBC-Derived, Activating Antigen Carriers (SQZ AACs) Prime Potent T Cell Responses and Drive Tumor Regression In Vivo
SQZ Activating Antigen Carriers (AAC) were derived from red blood cells (RBCs) and engineered to direct tumor-specific antigens and adjuvant to endogenous professional APCs, which subsequently activated T cell responses in vivo
In TC-1 tumor bearing mice, a model of HPV16+ cancers, AACs demonstrated a synergistic therapeutic effect in combination with cisplatin, a common chemotherapy used in many clinical settings
Median survival of mice increased in all combination treatment cohorts compared to single agent cisplatin or ACC treatment
Poster #211: SQZ eAPCs Generated from PBMCs by Delivery of Multiple mRNAs Encoding for Antigens, Costimulatory Proteins, and Engineered Cytokines
SQZ Enhanced Antigen Presenting Cells (eAPC) derived from peripheral blood mononuclear cells (PBMCs) and engineered with various mRNA encoding for multiple target antigens and immuno-stimulation signals, including CD86 and membrane bound IL-2 and IL-12, generated robust T cell responses in human in-vitro models
HPV16-encoding mRNA delivery to PBMCs stimulated CD8+ T cells across a range of HLA haplotypes, supporting future eAPC clinical development in broad HPV16+ patient populations
eAPC data highlights the potential to expand the therapeutic impact across tumor types by changing the antigen-encoding mRNA
Poster #165: Generating Enhanced Tumor Infiltrating Lymphocytes through Microfluidic Cell Squeezing
Cell Squeeze delivery of mRNA encoding membrane bound IL-2 (mbIL2) and IL-12 (mbIL12) into expanded tumor reactive CD8 human tumor infiltrating lymphocytes (TILs) from AgonOx* (AGX-148) demonstrated high levels of membrane-bound cytokine expression in vitro
Enhanced TILs proliferated independent of exogenous IL-2 and demonstrated improved granzyme B levels, illustrating the potential to eliminate systemic IL-2 administration in the clinical setting.
In an in vitro co-culture model with matched human melanoma cells, enhanced TILs demonstrated increased tumor killing as compared to un-modified TILs
* AgonOx, Inc. is a biotechnology company with a close alignment with the Earle A. Chiles Research Institute at the Providence Cancer Institute in Portland, OR.