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SEAKER cells coordinate cellular immunotherapy with localized chemotherapy.
1Massachusetts General Hospital Center for Cancer Research, Boston, MA, USA; Massachusetts General Hospital Department of Pathology, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Trends in Pharmacological Sciences
|May 1, 2022
Summary
New SEAKER cells combine chimeric antigen receptor (CAR) T cell therapy with a prodrug-activating enzyme. This dual approach enhances cancer attacks by overcoming tumor antigen escape and T cell dysfunction.
Area of Science:
- Immunotherapy
- Cancer Biology
- Synthetic Biology
Background:
- Chimeric antigen receptor (CAR) T cell therapy faces limitations due to tumor antigen escape and T cell dysfunction.
- These challenges hinder the effectiveness of current CAR T cell treatments in eradicating tumors.
Purpose of the Study:
- To engineer a novel cell therapy approach to overcome limitations in CAR T cell therapy.
- To develop synthetic enzyme-armed killer (SEAKER) cells for a combined immunologic and pharmacologic attack against tumors.
Main Methods:
- Engineered SEAKER cells to coexpress a CAR and a prodrug-activating enzyme.
- Designed SEAKER cells to target tumor sites for a localized therapeutic effect.
Main Results:
- SEAKER cells demonstrated a dual mechanism of action, combining CAR-mediated T cell activation with enzyme-mediated prodrug conversion.
- This dual attack strategy is designed to enhance efficacy against tumors resistant to conventional CAR T cell therapy.
Conclusions:
- SEAKER cells represent a promising advancement in immunotherapy by integrating cellular and enzymatic functions.
- This innovative approach holds potential for improving treatment outcomes for patients with difficult-to-treat cancers.
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