SQZ Biotechnologies Presents Preclinical SQZ® TIL Data Supporting Potential Ability of mRNA-Driven IL-2 and IL-12 Expression to Eliminate Need for Toxic Preconditioning and Systemic IL-2 Administration for Certain T Cell Therapies
SQZ Biotechnologies (NYSE: SQZ) presented promising preclinical data on tumor infiltrating lymphocytes (TILs) at the ESMO Congress 2022. Engineered with membrane-bound cytokines IL-2 and IL-12, these TILs may eliminate the need for toxic preconditioning and IL-2 administration. Key findings include enhanced TIL proliferation, tumor cell killing, and markers associated with T cell memory. The data indicates potential for outpatient TIL therapy, enabling repeat dosing and combination treatments. This advancement could redefine current TIL therapies.
- TILs engineered with mbIL-2 and mbIL-12 showed >70% viability without external cytokine support for 5 days.
- Demonstrated 3.5-fold higher tumor cell killing compared to unmodified TILs.
- Upregulated CD62L markers indicating memory T cell reprogramming (>80% positive).
- More than 200% greater in vivo cell persistence than unmodified TILs.
- None.
TILs Engineered to Temporarily Express Membrane-Bound IL-2 and IL-12 Could Potentially Improve TIL Function While Simultaneously Eliminating the Need for
Data Presented at ESMO 2022 Show SQZ® TILs Enhanced Proliferation In Vitro and In Vivo, Increased Tumor Cell Killing, and Upregulated Markers Associated with T Cell Memory
SQZ® TILs May Enable Repeat Dosing and Early Line Use of TIL Therapy in Oncology
“TIL therapies have shown exciting clinical results in solid tumors, but to overcome engraftment and persistence challenges they also require lymphodepletion and systemic IL-2, which are toxic to patients and prevent repeat dosing,” said
The SQZ® TIL platform draws from the company’s mbIL-2 and mbIL-12 constructs used in its enhanced Antigen Presenting Cell (eAPC) clinical trial. Both approaches are designed to take advantage of transient expression of membrane-bound cytokines so that potent cytokines such as IL-12 can be expressed without systemic toxicities. Additional TIL engineering with membrane-bound IL-7 (mbIL-7) and BCL-2, an anti-apoptotic factor, may further enhance the abilities of SQZ® TILs to engraft without preconditioning.
Major Findings from
Poster #761: Tumor Infiltrating Lymphocytes Expressing Membrane-Bound IL-2 and IL-12 Exhibit Enhanced Proliferation, Function, and Persistence Without Requiring Exogenous IL-2 Support
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Cytokine Expression and Function: TILs engineered with mbIL-2 and mbIL-12 induced high levels of expression and supported >
70% viability in the absence of external cytokine support for 5 days, a time greater than IL-2 is typically dosed in the clinic after TIL infusion. The membrane-bound cytokines produced an almost 4-fold expansion in vitro, which was comparable to unmodified TILs cultured in IL-2 containing media - Tumor Cell Killing: TILs from primary solid tumors engineered with mbIL-2 and mbIL-12 and subsequently cultured with donor-matched tumor cell lines showed 3.5-fold higher IFN-y release than the current clinical standard of unmodified TILs with exogenous IL-2, as well as increased tumor killing as measured by staining of apoptotic cells
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Memory T Cell Reprogramming: TILs engineered to express mbIL-2 and mbIL-12 upregulated CD62L, a classical marker of central memory T cells (>
80% positive, vs <20% positive for unmodified TILs at day 6). CD62L remains upregulated even after cytokine expression has diminished, suggesting a potential reprogramming of the TILs to a more memory-like state, which could positively impact T cell survival and clinical benefit -
In Vivo Survival and Phenotype: mbIL-2 and mbIL-2/12 TILs adoptively transferred into a mouse model each showed more than
200% greater cell persistence in vivo as compared to unmodified TILs, and mbIL-12 drove a 3.5-fold enrichment in CD62L expression in vivo out to at least day 5 post-transfer - Promising Targets: TILs engineered with mbIL-7 and BCL2, which can support cell survival, demonstrated a strong advantage in the absence of exogenous cytokine support and could serve as potential future TIL enhancers
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Media:
erin.phelps@sqzbiotech.com
857-760-0920
Investor:
michael.kaiser@sqzbiotech.com
857-760-0398
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FAQ
What preclinical data was presented by SQZ Biotechnologies regarding TILs?
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