T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with suboptimal overall prognosis. In recent years, remarkable advances in chimeric antigen receptor T-cell (CAR-T) therapy for B-cell malignancies have inspired growing interest in applying CAR-T to T-ALL. CD7-targeted donor-derived CAR-T therapies have demonstrated high complete remission (CR) rates in T-ALL; however, complications such as graft-versus-host disease (GVHD) and infection remain major challenges.

Autologous CD7 CAR-T therapy holds promise for reducing GVHD risk, but remains rare globally. Dr. Jing Pan of Beijing Gaobo Hospital shares key insights into the clinical development and rationale for autologous CD7 CAR-T therapy without T cell pre-selection in pediatric patients with relapsed/refractory (R/R) T-ALL.

1. Your team has conducted several studies on donor-derived CD7 CAR-T therapy in R/R T-ALL with encouraging results. What prompted you to explore autologous CD7 CAR-T therapy without T cell pre-selection in these patients?

Dr. Jing Pan: Since 2019, our team has actively explored CAR-T therapies for T-cell malignancies. In clinical practice, we've observed that many patients with T-lineage malignancies are unable to provide enough normal T cells for autologous CAR-T production, limiting success rates.

We also conducted multiple clinical trials using donor-derived CD7 CAR-T cells in T-ALL and T-LBL (T-lymphoblastic leukemia/lymphoma), which achieved high remission rates. However, risks of GVHD and infection increased significantly.

This led us to refine our approach—developing tailored CAR-T strategies based on patient profiles. For newly diagnosed or less heavily pretreated T-ALL patients, sufficient healthy lymphocytes can still be collected. For them, we began producing autologous CD7 CAR-T cells.

One major global challenge is product contamination: tumor cells in T-ALL are themselves T cells, making it difficult to isolate healthy cells for CAR-T manufacture. Many researchers attempt to overcome this by selecting for non-tumor T cells using specific sorting criteria.

However, we found that T cells with pre-selection often had lower viability and quality compared to those that were not pre-selected. Furthermore, many patients do not meet the criteria for selection, making them ineligible for trials and limiting the clinical reach of CAR-T therapy.

Our key insight was this: if tumor burden in peripheral blood is kept within a controllable range, the risk of contaminating the CAR-T product is very low—even without pre-selection. Based on this, we initiated a phase I clinical trial to explore the feasibility and safety of unselected autologous CD7 CAR-T therapy in R/R T-ALL.

Notably, none of the CD7 CAR-T products in this trial were contaminated. The clinical efficacy was comparable to our previous donor-derived CD7 CAR-T results, while the risk of GVHD and infection was significantly lower. This reinforces the need for individualized treatment strategies, even within the same disease subtype.

2. Compared to donor-derived CD 7 CAR-T therapies, international studies on autologous CD7 CAR-T are limited. What challenges exist in producing these cells for R/R T-ALL?

Dr. Jing Pan: The primary challenge lies in identifying suitable patients. Many with T-ALL or T-LBL relapse after intensive chemotherapy and have very low lymphocyte counts, making autologous CAR-T production technically difficult.

3. This study has preliminarily demonstrated the feasibility of autologous CD7 CAR-T therapy without T cell pre-selection in pediatric R/R T-ALL. How would you evaluate its safety and efficacy?

Dr. Jing Pan: Overall, the clinical efficacy and safety outcomes of this early-phase study met our expectations. Importantly, the findings suggest this approach is viable for certain patients and warrants further exploration.

4. Based on current findings, what are the remaining challenges in using autologous CD7 CAR-T therapy without T cell pre-selection in R/R T-ALL? Are the results applicable to heavily pretreated or high-burden patients?

Dr. Jing Pan: The concept of “non pre-selection” is gaining global attention, and we expect more institutions will engage in related research.

However, patients who have undergone multiple lines of chemotherapy typically have diminished lymphocyte reserves. Even without selection, manufacturing autologous CAR-T for them remains difficult and may yield less favorable outcomes. We strongly advocate for early cryopreservation of peripheral blood lymphocytes—ideally within three months of diagnosis in high-risk T-ALL or T-LBL—when immune function is relatively preserved. This ensures patients retain the option of autologous CAR-T therapy later, though it does not imply that every patient must pursue it.

5. What are your next research priorities?

We are actively addressing three key areas:

1. Comparative Analysis:
   We are running three cohorts to directly compare the efficacy and safety of autologous CD7 CAR-T, donor-derived CD7 CAR-T, and post-transplant CD7 CAR-T therapy.
2. Dose Optimization:
   Following the FDA’s 2022 “Project Optimus” initiative to reform dose selection in oncology drug development, we plan to determine the minimum effective dose of autologous CD7 CAR-T, reducing toxicity while maintaining clinical efficacy.
3. T-lineage Tumors with Mediastinal Masses:
   These patients still lack optimal therapeutic options. We aim to explore targeted CAR-T strategies to improve outcomes in this subgroup.