Bispecific-antibody-armed, metabolically enhanced headless CAR T cells: Safe and effective serial killers of solid tumors

Until now, chimeric antigen receptor (CAR) T cells immunotherapy has had limited success with solid tumors.

The major challenges have been T cell exhaustion, off-tumor toxicity, cytokine release syndrome (CRS), and metabolic insufficiency of CAR T in the immunosuppressive tumor microenvironment (TME).

In this webinar, Dr. Archana Thakur, associate professor of medicine, will present metabolically enhanced headless CAR T (hCAR T) cells armed with bispecific antibodies (bsAbs) that were created in the 2021 study by Dr. Thakur and her colleagues at the University of Virginia and University of Pennsylvania.

The researchers generated armed hCAR T cells by transducing with the construct containing the transmembrane, the intracellular domain (ICD) of the co-stimulatory receptors, and the T cell receptor signaling-CD3 Zeta domains followed by arming with bsAbs.

The created metabolically enhanced, bsAb-armed hCAR T cells proved themselves as safe, effective serial killers of tumor targets, secreting Th1 cytokines and chemokines, and continuing to kill under in vitro hypoxic condition.

Key learning objectives

• BsAb-armed hCAR T cells are superior to non-genetically modified T cells armed with bsAbs and mediate superior levels of cytotoxicity directed at all tested solid tumor lines
• The hCAR T cells killed multiple tumor lines significantly better than control T cells and secreted Th1 cytokines/chemokines at effector to target ratio (E:T) of 2:1 or 1:1
• HER2 hCAR T cells serially killed tumor targets up to 14 days and continued to kill under in vitro hypoxic conditions
• Sequential targeting of positive tumors showed significantly increased cytotoxicity compared to single antigen targeting
• In this study, the researchers used Agilent Seahorse XF, Agilent xCELLigence RTCA, and Agilent NovoCyte Flow Cytometer

Who should attend?

• Cancer researchers
• Lab managers
• Principle investigators
• Staff scientists
• Scientific directors
• Professors

Certificate of attendance

All webinar participants can request a certificate of attendance, including a learning outcomes summary, for continuing education purposes.