Cell therapy in solid tumors: Breakthroughs, delivery challenges, and what’s next

Cell therapy has reshaped oncology for patients with blood cancers, offering remission in conditions once considered incurable. Yet for solid tumors—which account for more than 90% of all cancers including breast, lung, colorectal, and pancreatic—replicating that success has proven far more elusive. Hematologic malignancies like acute lymphoblastic leukemia and lymphoma benefited early from CAR-T therapy’s direct access to circulating cancer cells. Solid tumors, however, present a different battlefield—one marked by physical barriers, immune-suppressive environments, and antigen complexity.

But the past two years have seen a dramatic uptick in research momentum. From China to the U.S., early-phase clinical trials are beginning to show measurable responses. Biotech companies, academic labs, and large pharma firms are now racing to turn these incremental wins into viable, commercial therapies. This article examines the progress so far, the technical and biological obstacles ahead, and the key players working to bring cell therapy to solid tumor indications.

What Are the Latest Breakthroughs in CAR-T Therapy for Solid Tumors?

A landmark trial conducted by Peking University offered the first glimpse of tangible progress. In a cohort of 266 gastric cancer patients, those treated with CAR-T cells experienced an average overall survival of 7.9 months—substantially longer than the 5.5 months seen in the standard care arm. Progression-free survival improved from 1.8 to 3.3 months. These numbers, while modest in absolute terms, are meaningful in the context of solid tumors, where prior CAR-T efforts had failed to demonstrate even basic durability.

The therapy, adapted from earlier designs pioneered by Dr. Carl June, uses a chimeric antigen receptor specifically tuned to gastric tumor antigens. It also incorporates safety switches and conditional activation mechanisms to limit off-target effects, an ongoing concern when dealing with solid tissue. More than 650 CAR-T programs are now in various stages of preclinical or clinical development globally, with many focusing on solid tumors such as lung, ovarian, pancreatic, and colorectal cancers.

Notably, researchers from the Netherlands Cancer Institute and institutions like MD Anderson Cancer Center have expressed cautious optimism. They highlight the use of dual-targeting CARs and armored CAR constructs—engineered to resist immunosuppression—as critical elements of the next generation.

Gilead Sciences, through its Kite Pharma subsidiary, is advancing a CAR-T platform for glioblastoma multiforme (GBM), one of the most aggressive and treatment-resistant brain cancers. Partnering with the University of Pennsylvania, the team developed CAR-T constructs targeting EGFRvIII and IL13Rα2, two well-known glioblastoma biomarkers. In early-stage clinical testing, 62% of patients with measurable tumors experienced radiographic shrinkage, with some sustaining disease stability for over 12 months.

The addition of a third targeting mechanism is now under development to address the problem of tumor antigen escape. Gilead’s decision to test this platform in newly diagnosed patients, rather than relapsed or refractory cohorts, suggests a growing confidence in its clinical viability.

Why Does Cell Therapy Still Struggle with Solid Tumors?

Despite promising trials, fundamental biological barriers continue to obstruct progress. Chief among them is the tumor microenvironment (TME), a hostile network of stromal cells, cytokines, and immune checkpoint proteins that actively suppress T-cell function. In hematologic cancers, CAR-T cells can circulate freely and locate their targets. In solid tumors, however, immune cells must first penetrate dense extracellular matrices and evade suppressive cells such as tumor-associated macrophages and regulatory T-cells.

Antigen heterogeneity further complicates treatment. Unlike leukemia cells that express uniform targets like CD19, solid tumors often express a patchwork of antigens that vary across patients—or even within a single tumor mass. This variability allows tumor cells to escape detection and regrow despite partial response to treatment.

Another major concern is cell persistence. Engineered T cells often fail to survive long enough within the solid tumor environment to mount a sustained attack. Researchers are therefore exploring targeted delivery systems—such as microneedle patches and biodegradable scaffolds—to enhance retention and site-specific activation of therapeutic cells.

What New Cell Therapy Strategies Are Being Developed for Solid Tumors?

To overcome these obstacles, researchers are layering multiple technologies. Tumor-infiltrating lymphocytes (TILs) have shown promise in early studies by directly sourcing immune cells from a patient’s tumor and expanding them for reinfusion. Obsidian Therapeutics is advancing OBX-115, a controllable TIL platform that uses a synthetic drug-inducible system to activate cells only in tumor environments. The company is currently testing this in advanced melanoma, with early data suggesting improved tumor control when used in combination with checkpoint inhibitors.

The U.S. National Cancer Institute is evaluating neoantigen-specific T-cell receptor (TCR) therapies in a Phase 2 trial targeting multiple solid tumor types. This approach involves isolating patient-specific tumor-infiltrating lymphocytes and transducing them with reactive TCRs, creating a highly personalized therapy.

Combination regimens are also gaining traction. Researchers are experimenting with concurrent delivery of CAR-T cells and PD-1 inhibitors, as well as oncolytic viruses and cytokine boosters, to modulate the tumor microenvironment and improve response durability.

How Are Cell Therapy Companies Tackling Manufacturing and Regulatory Hurdles?

Scaling cell therapies beyond hematologic use cases requires manufacturing innovation. Companies like Bionova Scientific and Cellares are leading efforts to automate and modularize CAR-T production. These platforms are designed to shorten turnaround time and ensure consistent cell quality—critical for any therapy aiming for broader adoption.

From a regulatory perspective, global agencies are stepping up. The U.S. Food and Drug Administration (FDA) has issued multiple RMAT designations for solid tumor-focused cell therapies, while China’s NMPA is piloting expedited pathways modeled after the U.S. system. Europe’s EMA has likewise begun releasing guidance tailored for advanced therapy medicinal products (ATMPs), particularly in the oncology space.

Investor interest has followed suit. Over $3.4 billion in global funding was directed toward CAR-T innovation in 2024, with significant allocations toward solid tumor programs. Public companies like Gilead Sciences (NASDAQ: GILD), Iovance Biotherapeutics (NASDAQ: IOVA), and Adaptimmune Therapeutics (NASDAQ: ADAP) are actively pursuing regulatory submissions or Phase 3 expansions.

Can Solid Tumor Cell Therapies Scale in 2025 and Beyond?

The future of cell therapy for solid tumors lies in integrated platforms that combine precision targeting, delivery enhancement, and immune modulation. Multi-antigen CARs, programmable TILs, and bispecific cell constructs are advancing from bench to bedside. AI-driven antigen discovery and simulation are improving target validation and helping reduce trial attrition.

Long-term success will also depend on logistics. Autologous therapies still face hurdles related to manufacturing time, patient-specific variability, and access delays. Allogeneic or “off-the-shelf” alternatives, though still experimental, may offer scalable options for broader populations—especially in health systems where turnaround time is critical.

As trial data matures and the first commercial approvals for solid tumor-directed cell therapies near reality, the oncology field may be on the verge of its next major inflection point.