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Study underway to evaluate novel T-cell therapy for hepatocellular carcinoma
An ongoing proof-of-concept clinical trial is underway to assess the use of a novel T-cell therapy for the treatment of advanced hepatocellular carcinoma.
“Traditional immunotherapy, such as checkpoint inhibitors, releases the brakes on the immune system, which allows it to attack the tumor but can also lead to attacks on other parts of the human body,” Daneng Li, MD, medical oncologist at City of Hope, said in a press release. “This approach engineers immune cells to directly attack a protein that is expressed in liver cancer. We are trying to individualize treatment for patients with advanced liver cancer.”
Advanced HCC is associated with poor prognosis and limited treatment options.
For this reason, investigators have initiated a phase 1/phase 2 clinical trial that involves the engineering of a patient’s immune T cells to target alpha fetoprotein (AFP)-peptide/HLA-A2 complex, a protein/antigen that is highly expressed in HCC.
Healio spoke with Li about how this therapy works, as well as the current trial and his hopes for its outcome.
Question: How does this therapy work?
Answer : Patients with hepatocellular carcinoma often overexpress AFP. This protein potentially is an attractive target for HCC treatment. ET140202 ARTEMIS (Eureka Therapeutics) is an engineered T-cell therapy for advanced HCC whereby autologous T cells are genetically modified to target the AFP-peptide and major histocompatibility complex.
Q: What is the role of T - cell therapy for solid tumors?
A: T-cell therapies for solid tumors are still in the early stages of development and clinical testing. These therapies have had tremendous success in hematologic malignancies, and we hope to translate that success to solid tumors.
Q: What have the challenges been with this approach in the past?
A: A concern with T-cell-based therapy in the past has been toxicity, such as cytokine release syndrome seen in patients with hematologic malignancies who received this type of therapy. However, as new T-cell-based therapies are established and designed for solid tumors, we have begun to make strides in reducing these side effects.
Q: What are the characteristics of the patients being treated?
A: For the current trial in HCC, patients must have advanced-stage disease that is classified as metastatic or locally advanced and surgically unresectable. Patients had to have progressed on or not tolerated at least one systemic line of treatment for advanced HCC. In addition, patients have to have high levels of serum AFP — their tumors are producing this type of protein — because the target of the treatment is AFP.
Q: How are you and your colleagues conducting the trial?
A: Once a patient has been identified as a good candidate for this type of therapy for HCC, the patient’s T cells are collected and modified to target the AFP-peptide/HLA-A2 complex on the patient’s tumor. The patient will undergo a conditioning chemotherapy regimen prior to infusion of the modified T cells, and then assessment and close monitoring to evaluate safety and efficacy of the T-cell treatment.
Q: What do you expect to find?
A: Our hope is to use this as a targeted approach for patients with tumors that overexpress AFP, and hopefully this will lead to a new treatment option for this vulnerable patient population.
Q: Is there anything else that you would like to mention?
A: The study is in the very early stages, so it will take some time before results are available. However, we are very excited that this novel therapy is offering a more individualized treatment approach for patients with HCC. We are hopeful that this will provide another key treatment option for patients diagnosed with this challenging malignancy. – by Jennifer Southall
For more information:
Daneng Li, MD, can be reached at City of Hope, 1500 E. Duarte Road, Duarte, CA 91010; email: danli@coh.org.
Disclosure : Li reports no relevant financial disclosures.