Our Science

Tackling solid tumors with cell therapy


Our Science

Tackling solid tumors with cell therapy

The Challenge

Our body’s immune system, specifically T cells, has the ability to recognize cancer cells as abnormal and kill them. Therapies based on genetically engineered patient-derived T cells have shown success in treating hematologic malignancies. But cell therapies have had limited success in solid tumors, which represent approximately 90% of cancers. Two primary barriers limit consistent and durable responses to cell therapy in solid tumors:

T-cell exhaustion

The dysfunctional state that T cells enter hindering their ability to respond to foreign antigens on cancer cells and eliminate them

Lack of durable stemness

This includes the inability of T cells to persist and self-renew to drive durable tumor cytotoxicity

T-cell exhaustion demonstration

A clinical study previously conducted at the Fred Hutchinson Cancer Center demonstrated that T-cell exhaustion is a major barrier to successful cell therapy in solid tumors. In this study, autologous ROR1-targeted CAR T cells infused into patients with chronic lymphocytic leukemia underwent rapid expansion and retained T-cell effector function, leading to tumor cell clearance and clinical responses. However, when CAR T cells generated with the same method were infused into patients with solid tumors such as triple-negative breast cancer or non-small cell lung cancer, these T cells often failed to expand adequately, rapidly upregulated cell surface markers of T-cell exhaustion and adopted a dysfunctional state.

Our Approach

At Lyell, it’s all about the cells. We are reprogramming T cells designed to outlast and eradicate solid tumors.

To achieve success in solid tumors, our cell therapies aim to:

Resist Exhaustion, Retain Function
Resist Exhaustion, Retain Function
Maintain cancer cell-killing ability in the immunosuppressive tumor microenvironment

Enhance Durable Stemness
Enhance Durable Stemness
Increase ability to self-renew and persist to drive durable tumor cytotoxicity

Our Technology

Our proprietary, stackable genetic and epigenetic reprogramming technologies are designed to create potent T cells with long-lasting functionality.

Genetic Reprogramming Technologies

Lyell’s genetic reprogramming technologies are designed to delay T-cell exhaustion and create more potent T cells with enhanced, durable antitumor activity in the immunosuppressive tumor microenvironment. Our technologies target the activator protein 1 (AP-1) transcription factor pathway, which plays a key role in T-cell effector function.


Reprogramming T cells through c-Jun overexpression delays exhaustion and results in increased proliferation, sustained cytokine production, and durable antitumor activity.


Combining NR4A3 KO with c-Jun overexpression further reduces T-cell exhaustion, leading to improved antitumor activity.

Epigenetic Reprogramming Technologies

Our epigenetic reprogramming technologies are designed to improve the stemness, persistence and function of T-cell products without gene editing.


Our Epi-R™ manufacturing protocols include proprietary media, optimized cytokine composition and well-defined cell activation and expansion protocols. Epi-R is designed to consistently and reliably generate populations of stem-like T cells with improved proliferation, antitumor activity, and reduced exhaustion.


Our Stim-R™ technology enables precise and optimized delivery of immune-activating molecules during T-cell production, in a way that more closely mimics the body’s natural process. This technology is designed to allow for greater control over T-cell stimulation and expansion, resulting in the generation of more potent T-cell products.


T-cell function declines as a person ages. Our rejuvenation technology has shown the potential to “turn back” the epigenetic clock to generate more stem-like T cells with reduced epigenetic age and enhanced proliferation ability.


We welcome collaborations. To speak with a member of our team, contact us at businessdevelopmentlyell.com.