CAR T-cell therapy shows vaccine effect in child with advanced sarcoma .

Texas Children's Hospital, Houston



October 14, 2020

3 min read

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The prognosis typically is poor for patients with metastatic rhabdomyosarcoma.

However, for one 7-year-old-boy with this form of muscle cancer, treatment with an investigational chimeric antigen receptor T-cell therapy plus a lymphocyte depleting chemotherapy regimen resulted in complete remission at more than 20 months of follow-up.

Meenakshi G. Hegde, MD, assistant professor of pediatric hematology-oncology at Baylor College of Medicine and Texas Children’s Hospital.

Healio spoke with Meenakshi G. Hegde, MD, assistant professor of pediatric hematology-oncology at Baylor College of Medicine and Texas Children’s Hospital and lead author of a case study on the child, who received the regimen in the HEROS 2.0 trial.

Hegde’s team found evidence that this novel CAR-T cell regimen acted like a vaccine, helping recruit the immune system to attack the child’s tumor.

Hegde explained how researchers applied lessons learned from a previous trial to HEROS and what makes this child unique among those treated in the study.

Question: Can you explain the rationale for this approach?

Answer: The phase 1 trial in which this child was enrolled was designed to target the HER2 protein molecule on the surface of sarcoma cells. In contrast to blood cancers, the proteins that we target in solid tumors such as sarcomas are not present on the surface of all tumor cells. In addition, when present they have a variable intensity in terms of their expression, which makes it difficult to eliminate all of the cells in the tumor with targeted therapies.

Based on our prior experience, we developed a treatment plan with multiple CAR T-cell infusions preceded by chemotherapy. However, it is important to note that the chemotherapy in this regimen was not intended to kill the tumor cells, but instead to create space for the therapeutic CAR T cells infused into the patient.

Q: What makes your approach novel compared with other CAR T-cell therapies?

A: This approach has been used with other investigational CAR T-cell therapies, but usually only as a one-time procedure. The single-infusion approach has shown that the CAR T cells fail to persist long enough to have any clinically meaningful benefit.

So, we wanted to develop a method that achieved sustained levels of active CAR T cells over a longer period to attack the tumor. This regimen included three cycles of chemotherapy and CAR T-cell infusions (induction) followed by subsequent CAR T-cell infusions without chemotherapy (consolidation). During consolidation, the T cell numbers were monitored closely, and repeat CAR T-cell infusions were administered to maintain levels in the blood. We stopped the consolidation therapy at 6 months; however, 6 months later there was evidence of tumor regrowth. At the time of relapse, we repeated the treatment with CAR T cells plus lymphodepleting chemotherapy and again achieved a complete response. This time, we supported subsequent CAR T-cell infusions with the addition of pembrolizumab (Keytruda, Merck) to boost their anti-cancer activity. This child remains in remission 2 years after stopping T-cell infusions.

Q: What, if any, treatment-related toxicities did you observe?

A: The child developed low-grade cytokine release syndrome when CAR T cells were administered following lymphodepletion. The child also had low blood counts after the chemotherapy; however, there were no infections. During the consolidation therapy, CAR T cells were given in the outpatient setting without any toxicities.

Q: What about this patient’s response to therapy is unique?

A: This child’s sarcoma appeared to have expression of the HER2 protein on about 70% of tumor cells examined. Interestingly, following HER2-directed CAR T-cell infusions, we found evidence that the child’s immune system was recruited to attack the tumor. Our investigation showed that the tumor destruction initiated by CAR T cells may have “triggered” the immune system’s response to aid in fighting the tumor, which may have contributed substantially to the child having a complete response. This type of response is unique in the study of CAR T cells, which is why we submitted the report on this single patient to Nature Communications. We hope that the findings can be useful to other scientists and researchers going forward.

This recruitment of the immune system opens up a new concept that CAR T cells may be used almost like a tumor vaccine. However, whether this is unique to a certain disease state or patient is yet to be determined.

Q: Do your results have any potential to inform or impact clinical practice?

A: As far as becoming a standard of care, I don’t think CAR T-cell therapy is there yet for solid tumors. We must first treat a much larger number of patients to confirm benefit. Based on the actionable findings from our patient with an exceptional response, we are taking those next steps by incorporating immune checkpoint inhibitor with lymphodepletion and CAR T cells in our upcoming clinical trial.

For more information:

Meenakshi G. Hegde, MD, can be reached at Texas Medical Center, 1102 Bates Ave., Ste. 1570, Houston, TX 77030; email: