Decoding the Blueprint of Life: CAR-T as a Precision Navigation System Starting from Hematologic Malignancies
In the vast landscape of cancer immunotherapy, CAR-T cell therapy represents a transformative innovation. According to Dr. Changsong Qi of Peking University Cancer Hospital and Beijing GoBroad Hospital, its remarkable efficacy in hematologic malignancies stems from highly specific tumor-associated antigens such as CD19 (in acute lymphoblastic leukemia) and BCMA (in multiple myeloma), which serve as precise "navigation systems" for T cells.
"Essentially, the CAR construct reprograms T cells, enabling them to identify and eliminate tumor cells," explained Professor Qi. Once reinfused, these engineered T cells are able to precisely target and destroy tumor cells expressing these markers, achieving high response rates and sustained immune surveillance — a principle now validated by multiple commercial products and national regulatory frameworks.
The Challenge of Solid Tumors: Redefining the Role of CAR-T Therapy
Compared with hematologic cancers, the treatment of solid tumors is significantly more challenging, primarily due to:
- The lack of ideal, broadly expressed tumor-specific targets
- A highly immunosuppressive tumor microenvironment
- Tumor heterogeneity and antigen escape
“We initially explored targets like EGFR, but early studies showed an objective response rate of less than 10%, coupled with severe toxicity,” Professor Qi acknowledged. However, breakthroughs have since emerged with novel targets in solid tumors — including Claudin18.2 (gastric cancer), GPC3 (hepatocellular carcinoma), and GUCY2C (colorectal cancer).
Claudin18.2 has proven to be one of the most promising targets in gastric cancer, with expression in nearly 60% of moderate-to-high Claudin18.2-positive cases. CT041, a CAR-T product developed against this target, has entered Phase II clinical trials. Among over 200 patients treated, the objective response rate has consistently ranged between 40–50% — more than tenfold higher than the 2–5% seen with third-line standard treatments.
In liver cancer, GPC3 is expressed in approximately 70% of hepatocellular carcinomas and is nearly absent in normal tissues, making it an ideal “window target” for CAR-T therapy. New generations of structurally optimized GPC3-CAR-T products have achieved objective response rates exceeding 70% in mid-to-high dose cohorts, significantly prolonging median survival.
For colorectal cancer, GUCY2C (also known as GCC) shows stable expression in 60–70% of patients across both primary and metastatic sites. Professor Qi's team is collaborating with industry partners to advance CAR-T products targeting GUCY2C, with early studies showing objective response rates of approximately 40%.
Innovative Delivery Routes: Paving the Way for CAR-T Cells to Reach Solid Tumors
A key determinant of CAR-T efficacy lies in the ability to physically deliver cells to tumor sites. “Traditional intravenous infusion often proves inadequate for certain locations,” Professor Qi emphasized. “Targeted delivery strategies are essential.”
Several innovative administration routes are currently being explored in clinical settings:
- Intraventricular injection: For intracranial tumors like neuroblastoma, CAR-T cells are infused directly into the brain ventricles to bypass the blood-brain barrier, enhance local effects, and minimize systemic toxicity.
- Hepatic arterial infusion: Especially for liver cancers expressing GPC3, CAR-T cells are delivered through the hepatic artery to achieve high local concentrations.
- Peritoneal/pleural infusion: Applicable to peritoneal metastases or thoracic tumors to maximize local efficacy.
In combination with debulking surgery, these approaches reduce tumor burden and improve the tumor microenvironment, ultimately enhancing CAR-T cell persistence and function.
Clinical Cases: Witnessing the Power of a “Living Drug”
Dr. Qi shared several compelling clinical cases that vividly illustrate the life-altering potential of CAR-T therapy as a “living drug”:
- A gastric cancer patient with anastomotic recurrence who was unable to eat regained the ability to consume porridge within just over a week following Claudin18.2-CAR-T infusion. One month later, rapid tumor regression even triggered bleeding — a dramatic confirmation of CAR-T's potent cytotoxicity.
- Another patient, previously fully reliant on parenteral nutrition due to complete obstruction, resumed oral intake just seven days after treatment and went on to enjoy over two years of high-quality life.
- A woman in her 30s, suffering from peritoneal metastases, renal failure, and carrying four drainage tubes, had all tubes removed within six months post-treatment and returned to work.
These examples demonstrate that CAR-T therapy is evolving from an experimental intervention into a modality capable of reconstructing lives.
Common Questions Answered: Helping More Patients Take the First Step
At the end of the interview, Professor Qi addressed several of the most pressing questions raised by patients:
On eligibility for clinical trials:
“Not all patients can enter clinical studies immediately,” he emphasized. “Target antigen testing is essential. Only when expression is confirmed can tumor burden and metastatic status be evaluated for trial inclusion.”
On 'pseudo-progression' post-treatment:
Some patients may initially show tumor enlargement on imaging. This is often due to CAR-T cell infiltration and inflammation rather than true disease progression. Imaging density and clinical symptoms are key to distinguishing between the two.
On timing and treatment duration:
“Unlike chemotherapy, CAR-T therapy involves a single infusion,”Professor Qi explained. “If the patient is stable, we recommend allowing time for the cells to act, rather than rushing into further treatment decisions.”
Closing Words: From Breakthrough to Cure, the Future of CAR-T Therapy Is Worth Pursuing
Dr. Qi concluded with an encouraging message:“Today, we are no longer content with simply prolonging survival — we are striving for true functional cures. CAR-T therapy is opening up new possibilities in the treatment of solid tumors. As long as we keep exploring and hold on to hope, the dawn of better outcomes will surely come.”
